analysis of cost drivers and trends in the blood sector of cost drivers and trends in the blood...

Analysis of Cost Drivers and Trends in the Blood Sector

For the Department of Health and Ageing

August 2011

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About Sapere Research Group

Sapere Research Group is one of the largest expert consulting firms in Australasia. We are a leader in provision of independent advice on public policy, public sector management and strategy, economic analysis and forensic accounting services. Sapere provides strategic advice, independent expert testimony and other advice to decision‐makers in Australasia’s government agencies, regulatory bodies, private sector corporations and major law firms. Sapere Research Group previously traded in the Asia‐Pacific region as LECG Limited.

For information on this document please contact:

Name: Ian Haupt

Telephone: 02 6263 5941

Mobile: 0419049511

Email: [email protected]

Sydney Level 14, 68 Pitt St GPO Box 220 Sydney NSW 2001 Ph: + 61 2 9234 0200 Fax : + 61 2 9234 0201

Canberra Level 6, 39 London Circuit PO Box 266 Canberra City ACT 2601 Ph: +61 2 6263 5941 Fax: +61 2 6230 5269

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Wellington Level 9, 1 Willeston St PO Box 587 Wellington 6140 New Zealand Ph: +64 4 915 7590 Fax: +64 4 915 7596

Auckland Level 17, 3‐5 Albert St PO Box 2475 Auckland 1140 New Zealand Ph: +64 9 913 6240 Fax: +64 9 913 6241

CONTENTS

Acknowledgements .................................................................................................................................. i

Executive Summary ................................................................................................................................. ii

Trends in Demand for Blood and Blood Products ............................................................................. iv

Demand Drivers ................................................................................................................................ xii

Cost of Blood and Blood Products in Australia ................................................................................ xiii

Best practice—Appropriate Use ...................................................................................................... xvii

Future Trends .................................................................................................................................... xix

Key Findings ..................................................................................................................................... xxii

The Way Forward ............................................................................................................................ xxiii

Introduction ............................................................................................................................................ 1

Project Methodology .............................................................................................................................. 5

Literature Review ................................................................................................................................ 6

Data ..................................................................................................................................................... 6

Consultations ...................................................................................................................................... 6

Overview of Australian System ............................................................................................................... 8

Governance of the Australian Blood Sector........................................................................................ 8

Recent Reviews of the National Blood Arrangements ...................................................................... 10

National Blood Supply System .......................................................................................................... 11

Legislation, Guidelines and Standards .............................................................................................. 18

Stakeholders ..................................................................................................................................... 18

Funding ............................................................................................................................................. 20

Achievements in The Australian Blood Sector .................................................................................. 23

Use of Blood and Blood Products ......................................................................................................... 37

Data Considerations .......................................................................................................................... 37

Overview of Blood Use in Australia .................................................................................................. 39

What Drives Demand for Blood in Australia? ................................................................................... 40

Fresh Blood Products ........................................................................................................................ 46

Plasma Derived Products .................................................................................................................. 52

Recombinant Products ...................................................................................................................... 57

State and Territory Patterns of Blood Use ........................................................................................ 59

Usage Patterns Indicated by Hospital Separations ........................................................................... 75

Who Uses Blood and What is it Used For in Australia? .................................................................... 86

How Does Blood Use in Australia Compare Internationally? ......................................................... 100

Cost of Blood and Blood Products ...................................................................................................... 105

What are the ‘Costs’ Of Blood In Australia? ................................................................................... 105

Explicit Costs – The ‘Costs to Budget’ ............................................................................................. 105

Non‐Explicit Financial Costs – The ‘Transfusion On‐Costs’ ............................................................. 120

Full Economic Cost .......................................................................................................................... 125

Cost Drivers ..................................................................................................................................... 125

Best Practice Use................................................................................................................................. 130

Introduction .................................................................................................................................... 130

What Is ‘Appropriate Use’? ............................................................................................................. 130

Is Use ‘Appropriate’ In Australia? ................................................................................................... 133

Future Trends ...................................................................................................................................... 159

Outlook For Market Sustainability—Demand and Supply Dynamics ............................................. 159

Outlook for Product Prices .............................................................................................................. 173

Blood Forecast Model ..................................................................................................................... 177

References .......................................................................................................................................... 204

Acronyms and Abbreviations .............................................................................................................. 217

APPENDICES

Appendix 1: Terms of Reference

Appendix 2: Reference Group Participants

Appendix 3: Data Sources

Appendix 4: Persons and Organisations Consulted

Appendix 5: Research References

Appendix 6: Further Information on Data Sets related to BloodNet Proposal

Appendix 7: Price Assumptions for Blood Demand Model

Appendix 8: Scenario Data Tables

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Acknowledgements A task of this complexity and duration requires the cooperation and contribution of many people.

I would like to thank project team members, who worked with persistence and dedication long after they expected to be doing other things, and to those who made themselves available on numerous occasions to provide advice and assistance. They include Blair Alexander, Matt Balmford, Alan Bansemer, Anne Buttsworth, Peter DeGraaff, Shannon Farmer, Dr Axel Hofmann, David Marcus, Dr John Rowell, and Margaret Stewart.

Thanks must also go to staff of The Department of Health and Ageing (Barny Lee and Jane Spittle in particular), the National Blood Authority, State and Territory health agencies and the Blood Service for the generous assistance they have provided with this project. This includes the provision of data, as well as other information and perspectives.

Ian Haupt Project Director

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Executive Summary This is one of two projects commissioned by the Department of Health and Ageing (DOHA) to help inform the financial management of the blood sector in Australia.

The project analysed the trends in cost and demand for blood and blood products. This included an analysis of differences in demand across Australian states and territories and also comparisons (where possible) with similar countries. It also involved an assessment of the relationship between demand and indications of ‘best practice’ use of blood and blood products.

The overall project aim was to increase knowledge of the trends in demand and costs and cost drivers in the sector, so as to be able to predict with more confidence future costs and also to identify areas where governments may be able to act to manage more sustainably the growth in costs.

A further objective of the project was to predict future demand and costs to government. The report details the results of modelling to forecast future demand and costs for the next 25 years.

The project was undertaken in conjunction with a related project, Options to Manage Appropriate Use of Blood and Blood Products. Many of the information sources were common to both projects, including much of the literature, data sources and stakeholders. Findings and conclusions have consequently been drawn from both projects.

ACHIEVEMENTS IN THE AUSTRALIAN BLOOD SECTOR

The blood sector in Australia has seen significant progress over the last decade or so, particularly with the establishment of a national approach and cooperation among governments. The national approach gathered momentum with the creation of the Australian Red Cross Blood Service (the Blood Service) as a national body in 1995, the subsequent introduction of the Australian Health Ministers’ Advisory Council (AHMAC) Blood and Blood Products Standing Committee and, in 2003, the signing of National Blood Agreement among Australian governments and creation of the National Blood Authority (NBA).

The NBA’s achievements after its first five years of its operation (National Blood Authority, 2008) included establishment of:

contract management arrangements that delivered significant cost savings to all Australian governments;

a range of supply contingency provisions to prevent significant stock shortages;

governance frameworks to integrate blood into overall health sector risk planning;

effective relationships with key stakeholders;

safety and quality products such as the recent Initial Australian Haemovigilance Report (2008) and the Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) in Australia (2008) (‘the IVIg Criteria’).

NBA has also progressed data capture and analysis as well with the development, for example, of:

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the Australian Bleeding Disorders Registry (ABDR), which allows for more accurate planning of supply requirements for people with haemophilia and other bleeding disorders;

Integrated Data Management System (IDMS);

the first Blood Measures Guide, which was a world first in establishing a nationally accepted set of measures on the use and effectiveness of fresh blood components;

a national electronic ordering and receipting system (BloodNet), which is also planned to have enhanced data capture functions to assist sector planning and performance evaluation.

The current review of the clinical guidelines governing the use of blood components has been another significant development. While perhaps overdue, the resulting revised guidelines will provide the most contemporary evidence‐based information on when and how to use fresh blood components.

Since the introduction of the National Blood Agreement, states and territories have also made progress, including promoting efficiency in use of blood and blood products, reducing wastage and promoting best practice management and use of blood products, blood related products and blood related services. The report on Options to Manage Appropriate Use of Blood and Blood Products provides information on the initiatives, which the various jurisdictions have put in place. They have included:

establishment of the Blood Watch program, with its many initiatives targeting clinicians, but also patient education, in NSW;

establishment of BloodSafe in SA and Blood Matters in Victoria, again with multi‐faceted initiatives;

devolution of the state blood budget to public hospitals or Area Health Services (AHS), in NSW and Tasmania;

concerted waste minimisation strategies in Queensland and Tasmania;

development and implementation of the electronic ordering and receipting system (ORBS) in Queensland;

development and commencement of a state‐wide Patient Blood Management Program in WA, concentrating on use of blood components.

In terms of the safety record of the sector, the 2010 report of the Haemovigilance Advisory Committee (HAC) (2010) noted that ‘there is no evidence at this stage to suggest that the rate of transfusion errors in Australia is outside the range experienced in OECD countries.’ (Ibid.) The report indicated that ‘(i)n common with other OECD countries, such as the United Kingdom, New Zealand, Sweden and Canada, the risks to the safety of transfused patients in Australia were predominantly in the hospital environment, arising from procedural errors.’ (Ibid.) The 2008 report of the HAC had indicated that approximately 65 per cent of incidents reported in Australia had involved procedural errors and that this was ‘broadly compatible with (the results from) other OECD countries.’ (Ibid.) The UK SHOT Annual Report 2008 (Serious Hazards of Transfusion, 2008) indicated that procedural errors represented 59 per cent of cumulative numbers of cases reviewed in the period 1996‐2008.

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TRENDS IN DEMAND FOR BLOOD AND BLOOD PRODUCTS

In general, the absolute volumes of blood and blood products issued have been increasing over recent years1, and increases in costs have generally followed. Some distinct patterns in usage rates emerge from the data.

RATES OF GROWTH IN DEMAND

Growth in demand for the major fresh blood product, namely red cells, has been broadly in line with population growth, averaging 1.3 per cent per annum over the period 2003‐04 to 2009‐10. Average growth in demand for platelets and fresh frozen plasma (FFP) were 4.7 and 2.6 per cent respectively over this period.

In contrast, demand for certain plasma‐derived products has grown very strongly over the same period. For example, intravenous immunoglobulin (IVIg) issues grew by an average 12 per cent per annum, and Prothrombinex‐VF by 29 per cent and albumin by 9 per cent per annum.

FIGURE 1: FRESH BLOOD PRODUCT VOLUMES, 2003‐04 TO 2009‐10

Source: NBA National Supply Plan and Budget, 2003-04 to 2009-10

1 An exception is whole blood, the use of which has declined in favour of use of blood components (red cells, platelets etc) .

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FIGURE 2: SELECTED PLASMA DERIVED PRODUCT VOLUMES, 2003‐04 TO 2009‐10


VARIATIONS IN BLOOD PRODUCT USAGE AMONG JURISDICTIONS

A comparison of per population usage rates across different jurisdictions shows significant differences in patterns of use. For example,

South Australia’s use of red cells has been high relative to other jurisdictions (44 units per 1000 population in 2009‐10, against a national average of 36 units). Red cell use in NSW, at 35 units per 1000 population in 2009‐10, was lower than the other large states, Victoria and Queensland (at 38 units per 1000 population). These relativities have persisted over the period since 2005‐06 (which coincides with the introduction of Blood Watch in NSW).

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FIGURE 3: RED CELL ISSUES PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10

Source: NBA National Supply Plan and Budget, 2003-04 to 2009-10, ABS catalogue 3101.0 – Australian Demographic Statistics.

IVIg use per 1000 population in Queensland has been substantially higher than the other large states, and second only to Tasmania. For example, in 2009‐10, IVIg use in Queensland was 145 grams per 1000 population, compared with 129 and 112 grams per 1000 population in NSW and Victoria respectively. These relativities have been present since at least 2006‐07.

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FIGURE 4: USE OF IVIG PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10

Source: NBA National Supply Plan and Budget, 2003-04 to 2009-10, ABS catalogue 3101.0 – Australian Demographic Statistics

Prothrombinex‐VF use per 1000 population in Victoria stands significantly above the other large states. For example, in 2009‐10 it was 2.34 units2 per 1000 population, compared with 0.85 units per 1000 population in NSW and 1.24 in Queensland. Prothrombinex‐VF use has grown much faster in Victoria than the other jurisdictions over the period since 2004‐05.

2 Standard units of x500IU.

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FIGURE 5: PROTHROMBINEX‐VF VOLUME PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


Albumin use per population is highest in Queensland and significantly higher than in NSW. For example, in 2009‐10, it was 394 grams per 1000 population in Queensland compared with 263 in NSW.

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FIGURE 6: ALBUMIN ISSUES PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


Significant differences among jurisdictions were also evident in transfusion related hospital separations data. For example:

The proportion of all separations involving transfusion (excluding NT as an outlier) ranged from around 3.2 per cent in NSW and Tasmania, to around 4.2 per cent in South Australia in 2008‐09;

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FIGURE 7: PERCENTAGE CHANGES IN TRANSFUSED AND TOTAL SEPARATIONS BY JURISDICTION, 2003‐04 TO 2008‐09

Source: National Admitted Patient Care Collection, 2008-09, Department of Health and Ageing

Queensland stands out in terms of the number of separations per 1000 population involving transfusion of IVIg and platelets; SA in terms of the rate of transfusion of red cells and platelets; and Victoria in terms of the rate of separations involving transfusion of Other Serum3 and also IVIg;

The rates of transfused separations per population in NSW for red cells, platelets and IVIg are consistently and significantly lower than in the other large jurisdictions;

Tasmania experienced a reduction in transfused separations over the period.

3 Most likely to be attributable to albumin, as Victoria has a relatively low rate of FFP use per 1000 population based on volume of issue figures

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FIGURE 8: PROPORTION OF SEPARATIONS INVOLVING TRANSFUSION, BY JURISDICTION, 2008‐09


National transfused separations grew faster than total separations over the period 2003‐04 to 2008‐09. In 2008‐09, Queensland, South Australia and Victoria were above the national average in terms of the proportion of all separations involving transfusion.

FIGURE 9: TRANSFUSED SEPARATIONS PER 1000 POPULATION AS RATIO OF NATIONAL AVERAGE, SELECTED BLOOD PRODUCTS BY JURISDICTION, 2008‐09


On the whole, reliable explanations for the variations in jurisdictional usage patterns of blood and blood products were not able to be made from the data. It is not known whether the patterns follow differences in the profile of medical conditions, or differences in prescribing cultures.

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PRIVATE SECTOR TRANSFUSION RATES IN QUEENSLAND

Queensland was the only jurisdiction where the rate of transfused separations per bed in the private sector exceeded that in the public sector, and by a significant degree. The anomaly was reflected also in the rate of transfused separations per bed involving red cells, platelets, IVIg and other serum. That is, there was a higher proportion of private sector separations associated with transfusion of these products.

INTERNATIONAL COMPARISONS

Based on available data, Australia’s use of red cells (on a per population basis) lies towards the lower end of usage rates among member countries of the European Union. For example, in 2003, Australia’s red cell use per 1000 population was 37.1 units, while Germany, Denmark and Sweden all recorded rates of approximately 50 units or above.

In terms of the use of IVIg, however, Australia appears to be among the relatively higher use countries, along with Canada and the USA. For example, Australia’s use of IVIg in 2010 was approximately 121 units per 1000 population, compared with an estimated 60 units in New Zealand and 50 in the UK.

DEMAND DRIVERS

A range of factors influence the demand for blood and blood products. They include:

Demographic factors

Available evidence shows that older age groups tend to be higher users of fresh blood products. They most likely also consume higher rates of the major plasma derived products (particularly IVIg and Prothrombinex‐VF), given the indications for use of these products. However, information was not available to show this conclusively.

Rates and incidence of disease

Information was generally lacking in regard to the clinical uses for blood and blood products. However, what was available showed that red cells are most commonly used for haematology oncology, and surgical procedures, (particularly cardiothoracic surgery, orthopaedic procedures and organ transplants). Seventy per cent of IVIg use in 2009‐10 was attributed to five conditions: Acquired Hypogammaglobulinemia secondary to haematological malignancy; Chronic Inflammatory Demyelinating Polyneuropathy (CIDP); Primary Immune Deficiency; Myasthenia Gravis (MG); and Multifocal Motor Neuropathy (MMN).

Clinical guidelines and indicated uses for products

Demand for blood and blood products responds to the recommended uses as specified in clinical guidelines or clinical indications for particular products. The principle extant guidelines in Australia—the 2001 National Health and Medical Research Council (NHMRC)/Australian Society for Blood Transfusion (ASBT) Clinical Practice Guidelines on the Use of Blood and Blood Components —are currently under review by NBA and the Australian and New Zealand Society for Blood Transfusion (ANZSBT), under the auspices of NHMRC.

Clinician prescribing practices

It is the clinician who prescribes blood and blood products to the patient; so demand is influenced by clinician prescribing practice. This, in turn, is influenced by a range of factors, including:

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patient outcomes, that is concern for what is best for the patient;

peer practice, particularly the practice of others within the same medical specialty;

prescribing ‘culture’, which often pertains to individual institutions;

education and training, including vocational training;

knowledge and evidence, with the strength of this influence dependent upon access to information;

financial incentives.

Treatment technologies and techniques

Development of new treatment technologies can increase or decrease the demand for blood products. For example, the extension of laparoscopic surgical techniques to an increasing range of surgeries reduces bleeding and hence demand for blood. On the other hand, development of surgical treatments for previously inoperable conditions could increase demand. Horizon scanning information on treatment technologies and techniques affecting blood demand was not found for this project.

Policy decisions and programs

Government decisions, for example, to increase funding for elective surgery throughput, can expand the demand for blood products.

Wastage

Wastage is an issue particularly among fresh blood products, which have limited shelf lives. The expiry of products is a challenge to manage, particularly where stocks need to respond to emergency situations. Wastage drives up the demand for blood, and consequently costs. Where it can be minimised, it should be. Information on wastage of blood components in Australia is lacking. It is currently collected by the Blood Service from voluntary participant hospitals.

Inappropriate use of blood and blood products

To the extent that blood and blood products are used inappropriately, demand is artificially inflated. There is evidence of inappropriate use of red cells in particular in Australia (more below).

COST OF BLOOD AND BLOOD PRODUCTS IN AUSTRALIA

There are a number of cost elements in relation to blood and blood products, including:

the direct financial costs of blood and blood products, or ‘costs to budget’, as borne by the Australian Government and the States and Territories;

the indirect financial costs of administering blood, or what might be referred to as the ‘transfusion on‐costs’ and other budgetary items associated with blood and blood product supply and administration;

the full economic cost of supplying and administering blood and blood products, that is the explicit and non‐explicit financial costs as well as other socio economic costs.

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COSTS TO BUDGET

Total costs to budget of blood and blood products have been rising steeply in recent years. Growth in the nominal product cost of the national blood supply4 has averaged more than 11 per cent per annum since 2003‐04, with total expenditure reaching approximately $851 million in 2009‐10. In addition, governments bear other related costs, principally the in‐hospital costs associated with transfusion. Various studies have estimated these costs at two to five times the cost to budget of a unit of product dispensed.

Some notable cost trends emerge from the data:

fresh blood products have traditionally accounted for over half of the total product cost of the blood supply. Plasma derived products currently account for about one‐third of expenditure and recombinant products just under one‐fifth;

FIGURE 10: RELATIVE COSTS OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, 2009‐10.

Source: NBA National Supply Plan and Budget, 2009-10

the product cost of recombinant products increased relatively early in the period since 2003‐04. For the last five years, the relative proportions of the three main product groupings have remained largely the same in the national blood budget;

prices for blood and blood products in Australia are national prices. Hence differences at a jurisdictional level flow from differences in demand;

expenditure on red blood cells has grown by around 11 per cent per year over the period 2005‐06 to 2009‐10, contrasting with growth in volume of just around 1.3 per cent per year. Similarly,

4 The ‘product cost’ of supply of blood and blood products refers to the cost to governments for the purchase of the products only and does not include additional costs such as administrative expenses for the NBA or health authorities or, for example, the cost of the National Managed Fund.

53%

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expenditure on platelets has grown above the rate of growth in volume (11 per cent per annum compared to 5 per cent for volume):

: the rise in costs can mainly be attributed to the rise in the average price for these products since supply has shifted to leucodepleted products;

among the plasma derived group of products:

: total expenditure is dominated by IVIg, which has risen strongly over the period since 2003‐04, due mainly to growth in demand;

: expenditure on clotting factors has risen steeply since 2006‐07;

for recombinant products, there has been a significant rise in expenditure on recombinant Factor VIII (rFVIII) reflecting principally a rise in demand;

the nominal cost per capita for the national blood supply has risen by 75 per cent between 2003‐04 and 2009‐10.

NON‐EXPLICIT COSTS

The process cost of administering the transfusion within the hospital may be 2 to 5 times that of the product cost (Shander, 2010). A recent Australian study demonstrated that the cost of transfusion of a single unit of red cells, including acquisition costs, was about $700 (Thomson , 2009).

The cost of Medicare Benefits Schedule items related to the administration of blood and bone marrow and also to pathology functions, such as blood grouping, performed in the private health care setting were more than $43 million in 2009‐10.

The full economic cost of supplying and administering blood and blood products is the explicit and non‐explicit financial costs, in addition to other socio economic costs such as reduced quality of life due to transfusion related infections.

COST DRIVERS

Cost drivers arise from both supply side and demand side pressures. The demand side pressures are the demand drivers outlined above.

Fresh blood products are supplied by the Blood Service, a not‐for‐profit supplier.

Manufacturing Costs

Information on the manufacturing costs of fresh blood products shows that around 60 per cent of the cost can be attributed to the collection of blood. Testing accounts for around 25 per cent, with actual production and distribution of the products composing the minor proportions of total manufacturing cost.

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FIGURE 11: BREAKDOWN OF MAJOR COMPONENTS OF MANUFACTURING COSTS FOR FRESH BLOOD PRODUCTS

Source: Cost Attribution Rules for the ARCBS Output Based Funding Model, NBA

Keeping the blood supply safe from infectious diseases

Testing of blood is a significant part of fresh product manufacture. Development and implementation of new tests to respond to emerging diseases is a further cost. However, safety measures also reduce full economic costs. For example, the introduction of leucodepletion cost around $1 million in capital costs, but was expected to reduce other costs in the broader healthcare system by around $5 million. The main impact was expected to arise from the removal of the need for bedside filtration (Australian Red Cross Blood Service, Undated).

Prices

Fresh blood product prices have been rising faster than demand. Plasma derived and recombinant products are supplied by commercial suppliers. Some significant falls in prices have been experienced or negotiated in regard to Prothrombinex in 09‐10, albumin in 05‐06 and imported IVIg over the period 2003‐04 to 2009‐10. These price decreases have ameliorated the cost impact of growing demand for these products.

Donor Marketing & Collection

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FIGURE 12: PRICES(a) OF SELECTED BLOOD PRODUCTS, 2003‐04 TO 2009‐10

(a) Prices are per the following units: Albumin per 10g; IVIg per gram; other products are standard units. IVIg(D) represents domestically produced IVIg; IVIg(M) represents the pooled average of the two brands of imported IVIg products. Source: NBA National Supply Plan and Budget, 2003-04 to 2009-10

BEST PRACTICE—APPROPRIATE USE

‘Best practice’ (or ‘appropriate use)’ of blood and blood products is defined in the reports as:

adherence to current clinical practice guidelines;

use which promotes safe and effective patient outcomes.

AUSTRALIAN USE

There is evidence of a degree of inappropriate use of blood and blood products in Australia, as assessed against the current guidelines. Evidence of a lack of compliance with current clinical guidelines relates mainly to the uses of blood components, with the bulk of evidence pointing to problems with red cell use.

The report refers to evidence indicating a wide variation in the levels of compliance with the NHMRC/ASBT Clinical Practice Guidelines on the use of Blood Components (‘the NHMRC/ASBT Blood Components guidelines’) in relation to the clinical use of red cells. There is a similar, but smaller, amount of evidence that use of platelets and FFP does not have a high level of compliance with the guidelines.

Evidence also points to clinicians being relatively unaware of the body of evidence about the appropriate uses of red cells and associated risks. For example, a joint NBA‐NSW study in 2007 reported that many clinicians interviewed found it difficult to nominate the appropriate haemoglobin (Hb) levels to justify transfusion (Eureka Strategic Research, 2007). As well, all doctors interviewed for that study indicated that they would typically prescribe a minimum of two units of

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red cells. This is despite the NHMRC/ASBT Blood Components guidelines indicating that red cells should be dispensed one unit at a time, so that the patient’s response can be assessed.

The reported uses of IVIg fall overwhelmingly within the published guidelines, according to information compiled by the Blood Service.

Other blood products are variously covered by clinical guidelines, with some not at all (for example, albumin). Apart from IVIg, information on adherence to relevant guidelines was not found with regard to other blood products.

SAFETY AND EFFICACY

There have been significant gains made in Australia in securing the safety of the blood supply and in the handling and administration of blood and blood products. Notwithstanding this, there is a large and growing body of literature which questions the appropriateness of many common transfusion practices in terms of patient health outcomes. The main evidence relates to the use of red cells. The literature questions the efficacy of red cell transfusion in treating iron deficiency anaemia (IDA) in surgical patients. Concerns have also been raised about dosage‐dependent morbidity and mortality risks, and risks arising from the age of red cells at the time of transfusion.

For example, based on an exhaustive literature search on transfusion outcomes, the Scientific Committee of the 1st International Consensus Conference on Transfusion Outcomes (ICCTO) held in Phoenix, Arizona, in 2009 stated,

there is a paucity of evidence for benefit and a burgeoning literature demonstrating a strong association between transfusion and adverse outcomes (Society for the Advancement of Blood Management, 2009).

In a very recent article, Isbister (2011) concluded that,

…it is no longer acceptable to maintain a laissez faire approach and assume the benefits and accept the risks of allogeneic blood transfusion. Evidence has accumulated questioning RBC5 transfusion efficacy and establishing transfusion as a contributing risk factor for adverse clinical outcomes in many clinical settings. Acknowledging that most available data are observational and that rigorous evidence to establish risks and benefits is needed, we should no longer accept transfusions as the default decision when there is clinical uncertainty.

The reports acknowledge that most of the evidence put forward is founded on observational studies, rather than randomised control trials (RCT). In this regard, Isbister et.al. (Ibid.) point out,

…frequentist statisticians and clinicians demand evidence from randomised controlled trials (RCTs); however, causation for the recognised serious hazards of allogeneic transfusion has never been established in this manner, and

…the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes … from observational studies.

A large body of evidence concerns risks associated with the use of red cells for treatment of iron deficiency anaemia in surgical patients. The literature suggests that transfusion of red cells per se is

5 Red Blood Cell.

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a risk factor for increased mortality, intensive care unit (ICU) admission, increased length of hospital stay and morbidity, through increased incidence of infection and other adverse conditions.

The lack of evidence supporting the efficacy of use of red cells for treatment of iron deficiency anaemia is recognised in the recent NBA Patient Blood Management Guidelines: Module 2 ‐ Perioperative (Pre‐Public Consultation Draft version).

There is also evidence to show that these risks may not be well understood among clinicians. The 2007 NBA‐NSW study referred to above included interviews with senior clinicians and registrars, from metropolitan and regional centres, within four main specialties—cardiac, orthopaedic, gastroenterology and anaesthetic. It found that while all doctors could name some of the risks associated with transfusion, very few could name all unprompted. The study concluded that,

senior doctors had a high personal confidence in prescribing habits, with a general assumption that they represent best practice. This is often incorrect, yet there is a reluctance to recognise this even when presented with the guidelines.

A recent Australia paper by Grey et al (2008) revealed that marked variations in transfusion practice persist, highlighting poor clinician understanding of appropriate blood usage.

Consultations with stakeholders during the course of the project reinforced this finding about clinicians’ level of knowledge.

The problems of lack of knowledge and lack of understanding among clinicians of the risks associated with transfusion point, in part, to deficiencies with the information base. In some instances, the information is lacking and in other instances, the information is there, but inadequately transmitted to key decision makers. Gaps in the information base are taken up further below.

The report also refers to studies indicating that adverse patient outcomes may also be dose dependent, that is, the higher the volume of red cells transfused, the greater the risk of contracting infections and other conditions. They also refer to studies which have indicated that mortality and morbidity impacts associated with transfusion may be positively related to the age of red cells at transfusion.

FUTURE TRENDS

There are several key influences over the trends in demand and cost into the future.

DEMOGRAPHIC FACTORS—THE AGEING POPULATION

As indicated above, blood and blood product use correlates positively with age. In large part, this is attributable to the positive correlation between ageing and the medical conditions associated with use of fresh blood and plasma derived products6. Several studies indicate that older age groups account for the greater proportion of red cell use. Haematological cancers, associated with over 20 per cent of IVIg use in Australia in 2009‐10, are correlated with age. Taking ageing into account, the Blood Service projects IVIg demand to grow by an average 16 per cent per annum between 2010‐11 and 2019‐20. Another example is warfarin use, which influences the use of Prothrombinex, is common in cases of atrial fibrillation, a condition which correlates positively with age.

6 The pattern of use of recombinant products responds to changes in the population of people with haemophilia

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The general trend was also supported in the age‐related analysis of hospital separations associated with transfusion, with the 40 to 70 year old age group accounting for the majority of separations involving transfusion of platelets, coagulation factors, IVIg and ‘other serum’ (including FFP and albumin) and the over 70 year age group for the greatest proportion of separations involving transfusion of red cells.

At the same time as an ageing population puts upward pressure on the demand for blood and blood products, it puts pressure on the available pool of donors for blood supply. At present, blood donations policy is founded on voluntary donation between the ages of 16 and 70. An ageing population will reduce the pool of potential donors.

The dual pressures placed upon the supply of blood and blood products are encapsulated in the concept of the Total Transfusion Dependency Ratio (TTDR) ‐ that is the ratio of the non‐donating population to the donating population. The TTDR is predicted to rise steeply from 2010 onwards, for all jurisdictions in Australia. It is an international trend as well, with high human development index countries also experiencing ageing in their populations.

FIGURE 13: PROJECTED TOTAL TRANSFUSION DEPENDENCY RATIOS, AUSTRALIAN STATES AND TERRITORIES, 1990 TO 2040

Source: SRG projections using ABS catalogue 3222.0--Population Projections, Australia, 2006 to 2101, series B.

PRESSURES ON PRODUCT DEMAND

Further strong growth in demand for IVIg is already predicted, as indicated above. This could be enhanced by expanded clinical indications for use. There are a number of potential new indications for IVIg under active investigation, including Alzheimers Disease and Myocardial Infarction.

Australia already experiences a shortfall in plasma for fractionation to keep up with this level of demand and consequently imports finished product on an annual basis.

There are also risks presented by new and re‐emerging pathogens, which would restrict the pool of donors in the absence of relevant tests.

Furthermore, the possible shortening of the shelf life of red cells in response to recent research findings may out further pressure on their supply. A growing body of research is questioning impacts on patient outcomes related to the age of red cells older than 14 days at the time of

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transfusion. Data (albeit limited) from Pathology Queensland indicates that only 25 per cent of red cells might currently be released for transfusion by the age of 14 days.

BLOOD FORECAST MODEL

Future demand and the product cost of blood and blood products7 have been projected using the Blood Forecast Model developed as part of this project.

Within the model, price is indexed according to predicted price movements. For the purposes of the forecasts contained in the report, price movements are assumed to continue at the rates built into the current forward estimates.

Volume can be indexed in the model by a range of demand drivers, such as demographic factors, incidence of major blood‐using medical conditions, impact of policy decisions, and changes in indicated uses.

Several future demand scenarios were constructed for this report, for comparison and analysis. These included a baseline scenario, a continuation of historical trends and several growth scenarios for IVIg.

Under the baseline scenario, volume was indexed according to the population age profile of each state and territory, with an assumption made about age‐related usage rates of red cells, based on available data.

The total product cost of supply of blood products across all product groups (except diagnostic products) was estimated to be approximately $937 million in 2010‐11. Under the assumptions of the baseline scenario, these costs were expected to rise (in nominal prices) to around $1.6 billion in 10 years, $2.8 billion in 20 years, and $3.6 billion in the next 25 years (the end of the forecast period). Under current contribution arrangements, the Australian Government would fund 63 per cent of this expenditure, and states and territories 37 per cent.

TABLE 1: BASELINE SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $937 $1,207 $1,606 $2,124 $2,790 $3,630

Real Costs $937 $1,067 $1,255 $1,466 $1,703 $1,958

Source: Results Sapere Research Group Limited model, adjusted for inflation on basis of 2.5 per cent annual inflation as contained in the 2010 Intergenerational Report (Department of the Treasury, 2010)

The product cost of the national blood supply was forecast to grow in real terms, at an average of approximately 3 per cent per annum. Under the assumptions of the baseline scenario, the real cost to Australian governments for the national blood supply was expected to approximately double in 25 years.

The baseline scenario predicted that jurisdictions with the relatively younger age profiles will experience steeper rises in demand and costs over this time.

7 Excepting diagnostic products.

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KEY FINDINGS

Key findings were drawn from both the Analysis of Cost Drivers and Trends in the Blood Sector and Options to Manage Appropriate Use of Blood and Blood Products8.

SIGNIFICANT REFORMS ARE NEEDED

Notwithstanding the progress that has been made, significant reforms are needed to ensure sustainability of the blood sector in Australia

The reasons for this include the level of risk that persists to patient safety and quality of care from some common transfusion practices; the fact that demand for blood products may well outstrip supply; and because existing governance and support systems do not promote efficiency and sustainability.

Some common transfusion practices put patient wellbeing at risk

There is evidence indicating a degree of inappropriate use of blood and blood products in Australia, particularly in relation to the uses of blood components, with the bulk of evidence pointing to problems with red cell use. As well, there is a large and growing body of literature which questions the appropriateness of many common transfusion practices in terms of patient health outcomes, with the main evidence again relating to the use of red cells.

Demand threatens to outstrip supply

Under current patterns of use, Australia’s ageing population will increase the demand for blood and blood products, while concomitantly decreasing the available pool of donors to maintain supply. This situation may be exacerbated by other upward pressures on demand, such as the incidence of some diseases and expansion of indicated uses for certain blood products. Other factors, such as the emergence of new pathogens and the risk of a shortening of the shelf life of red cells due to health safety and quality issues, may add further pressures.

Costs are likely to continue to rise

As demand rises in the face of constrained supply, market forces will drive up prices. Competition for scarce resources in the economy, and lack of competition in the supply of commercially supplied blood products will contribute to the risk of price increases.

Expanded testing in the face of new pathogens will also increase unit prices. A shrinking donor pool may also put pressure on the costs of supply, for example through intensified marketing for donors; and/or a greater reliance on the (relatively more expensive) apheresis collection.

International demand for blood and blood products is also likely to rise as other developed economies experience ageing in their populations. This will create upward pressure on commercially supplied products.

Current governance and support structures constrain efficiency or sustainability

The information base in the sector is inadequate. It lacks routinely collected data on key aspects of blood and blood product usage, including, who uses it, how much is used, what is it used for (in a clinical sense) and levels of wastage. The level of usage attributable to the private and public sectors was not distinguishable. Hospitals and clinicians lack access to the data that would enable them to

8 See Project Methodology, p5.

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monitor their own performance against sector best practice. Data to enable adequate demand forecasting or benchmarking of appropriate use is also lacking.

Clinicians lack access to up to date information on best practice in transfusion. The NHMRC/ASBT Blood Components guidelines are under review, after ten years of operation. There was evidence of lack of awareness among clinicians of these guidelines.

Key pricing and funding arrangements present incentives, which impede efficient and sustainable growth. There is a lack of pricing signals to key consumption decision makers in the system. Blood and blood products are presented as ‘free’ goods to the majority of hospitals and clinicians in the system.

Payment arrangements for suppliers on the basis of product issued potentially create a bias towards oversupply of products. There is also a lack of emphasis on the assessment of cost effectiveness in the funding of products.

THE WAY FORWARD

THE AUSTRALIAN BLOOD SECTOR REQUIRES SIGNIFICANT REFORM TO ENSURE SUSTAINABILITY

The key requirements for the blood sector to ensure sustainability into the future are:

for the sector to become more patient‐centric;

for the blood supply chain to be demand driven;

for governance and support structures to promote sustainability.

The Australian blood sector must become more patient‐centric

Some common transfusion practices carry unsustainable risks to the safety and quality of patient care. The patient blood management (PBM) approach needs to become embedded in the sector, such that patients’ individual needs drive the decision regarding transfusion. PBM emphasises culture change and there will be substantial challenges in achieving this.

Patient Blood Management Programs (PBMPs) have typically been concerned primarily with the use of blood components. Their scope should be expanded to include all blood and blood products.

The four year, state‐wide trial underway in WA since 2008, and the National Patient Blood Management Program (NPBMP) being developed by NBA to facilitate the uptake of PBM best practice, provide a good basis for entrenching PBM approaches within the sector. These and other projects demonstrate that successful PBMPs incorporate the following features:

a focus on culture change in transfusion practice;

education and communication strategies tailored to the clinical groups in focus;

effective data collection and monitoring systems to underpin education and communication strategies, and also to facilitate monitoring and evaluation, continuous improvement and risk management.

As the majority funder of the budgetary cost of blood and blood products, it is in the Australian Government’s interest also to consider financial incentives for PBMPs to be implemented.

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PBM needs also to be embedded in the private sector, which accounts for around one third of transfusion related separations nationally. This will require establishment of an information base on which to assess the extent of inappropriate use, and ultimately to design, implement and evaluate PBMPs. It will also require the creation of an appropriate incentive structure, such as the introduction of price signals.

Clinicians need a better understanding of the evidence base. The effectiveness of clinical guidelines needs to be improved and uptake should be encouraged within PBM settings. Patients should also be better informed of their risks and choices through informed consent processes and information campaigns.

The blood supply chain must be demand driven

Demand threatens to outstrip supply in the sector in the future. The supply chain needs to be driven by an efficient level of demand, one that truly reflects patient needs. While difficult to achieve across different jurisdictional cultures and administrative architectures, the move to a demand driven system is imperative if supply is going to meet future demand.

A demand driven system needs to be supported by price signals, which create the incentive for economical use of blood and blood products. Extending price signals in the system, particularly to hospitals, would establish the basic set of incentives needed to align demand with patient need. This would discourage inappropriate use and wasteful practices and would encourage hospitals to invest in PBM. Indeed, officials in NSW and Tasmania indicated in consultations that one of the tangible benefits that had arisen from blood budget devolution had been the interest it had engendered among hospital management to support appropriate use strategies.

The national blood budget should be incorporated into the hospital casemix funding system. The national blood budget should also be devolved to public hospitals and mechanisms to provide effective price signalling to private hospitals should be developed. There will be different considerations within the jurisdictions, which may affect that rate at which this initiative could be implemented. For example, NSW, Tasmania and, from 1 July 2011, Queensland, already have devolved state blood budgets. This may give them a lead on successful devolution of the national blood budget.

Price signals should also be extended to the private sector, given that this sector is responsible for around one‐third of all transfused hospital separations. The incentive structures are different within the private sector and further consideration needs to be given to the best means for achieving the creation of appropriate price signals.

Suppliers should be paid by hospitals upon verified delivery against orders. This would remove the inherent incentive for oversupply. It would be efficient to transfer the responsibility for payment of suppliers from the NBA to hospitals.

The introduction of contestability into the supply chain should be considered. The high level of concentration of suppliers in the system may impede efficiency.

Governance and support arrangements should be restructured

The information base needs to be upgraded significantly to support patient care, as well as planning and management of demand and supply. Governments should require public and private hospitals to supply them with a minimum dataset that supports demand and supply management and evaluation of sector performance.

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All jurisdictions should be required under the National Blood Agreement to generate a minimum dataset informed by the Guide to the Set of Standard Measures for the use of Fresh Blood Components in Australia, developed (in draft) by NBA and the Blood Service (2009). The information should be required to be provided in such a way as to feed into BloodNet’s central database (NBA’s ‘Big Red’). Using the power under the National Blood Authority Act9, the NBA could require a similar minimum level of information from the private sector.

A demand driven system also needs to be supported by relevant information about blood and blood product use. Better communication of projected demand levels to inventory controllers and supply planners would drive greater efficiency.

Funding structures need to support sustainability. Against a background of rising costs to government for blood and blood products, it makes sense for governments to consider approaches that put a sharper focus on cost‐effectiveness and appropriate use. Existing processes that could be applied to, or provide models for, the blood sector include the MBS Quality Framework and the Pharmaceutical Benefits Advisory Committee (PBAC) processes.

There are two ways in which these approaches could be adapted to the blood sector:

assessing the cost‐effectiveness of funding for high cost blood components; and

regular reviews of funding and use of existing blood products.

Based on the evidence in this report, priority should be given to reviewing the use of Albumin as a substitute for saline; and to the use of red cells to treat iron deficiency anaemia. These approaches could also be applied to consideration of government funding for the use of IVIg, particularly where new application is proposed.

Given pressures on the pool of future blood donors, governments need to monitor the pressures on donations and consider the need for providing incentives to donors as a means of maintaining blood supply.

Payment authority for suppliers should shift to hospitals and NBA’s role should shift more towards the coordination, analysis and dissemination of information, which supports appropriate use of blood and blood products and supply efficiency.

The provisions of the National Blood Agreement needs strengthening or revision in a number of areas, consequent upon the options discussed above. The main areas are:

mandatory levels of information from jurisdictions to support system planning and management;

changes in funding arrangements, including the extension of price signals through the supply chain;

reconsideration of the policy aim of self sufficiency in the light of a demand driven system, and supply constraints.

9 National Blood Authority Act 2003, Part 2, 10.

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Introduction The Department of Health and Ageing contracted Sapere Research Group Limited (SRG) to conduct a blood sector research project entitled Analysis of Cost Drivers and Trends in the Blood Sector. This project will help inform Government considerations of how to fund and manage the Australian blood sector over the next decade.

The report has been commissioned in the context of the rising costs to government of blood and blood products. The product cost of supply of blood and blood products10 has increased on average at over 11 per cent per annum between 2003‐04 and 2009‐10. The project aims to determine what is driving these cost increases and to identify whether there are areas where governments could take action to reduce or contain costs. Governments’ ultimate aims are to increase the financial sustainability of the blood sector by containing costs but at the same time preserving the quality of patient outcomes.

The commissioning of the project reflects a desire on the part of governments for continuation of reform in the Australian blood sector. Following the Review of the Australian Blood Banking and Plasma Product Sector 2001, chaired by the Rt Hon Sir Ninian Stephen, a national partnership approach between the Australian Government and the states and territories was commenced. An intergovernmental agreement gave effect to changes to the sector including the establishment of the National Blood Authority (NBA) to undertake national supply planning and management of blood and blood products on behalf of Australian governments.

The project involves analysing the trends in cost and demand for blood and blood products, including analysis of significant differences in demand across Australian government jurisdictions and also involving comparisons with similar countries. Assessments of the relationship between demand and indications of ‘best practice’ have been considered. A further objective of the project is to predict future costs and, as requested, SRG has developed a model to forecast cost drivers and trends for the next decade. The overall aim is to increase knowledge of costs so as to be able to:

predict future costs better;

manage the growth in blood sector costs.

In terms of scope, ‘blood and blood products’ refers to:

all fresh, plasma‐derived and recombinant blood products as purchased on behalf of Australian jurisdictions by the NBA under the National Blood Agreement; and

imported IVIg where individual jurisdictions wish to purchase imported IVIg separately, under the Jurisdictional Direct Order arrangements under the Imported IVIg Standing Offer managed by the NBA.

The analysis covers blood usage in Australia and international comparisons of costs and trends. The analysis is limited to products or aspects of supply, demand and use where data are available. In terms of examining best practice or ‘appropriate use’ of these products, focus has been placed on products that are important in terms of overall costs, where information exists and where governments have scope for action. The scope of the forecast costs has been determined by the available data.

10 Excluding diagnostic products.

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Terms of reference for the project are at Appendix 1.

Descriptions of the main blood products included in this report’s analysis appear in Box 1.

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BOX 1: INDICATED USES FOR SELECTED BLOOD PRODUCTS

Red cells

Red cells (also called red blood cells, RBCs and packed cells) resuspended are given to increase the oxygen carrying capacity of the blood, for example, in patients with severe anaemia following major blood loss after trauma and surgery. Red cells are also used in elective settings to treat patients with severe anaemia—for example, patients with severe anaemia secondary to chronic disease, in the setting of chemotherapy and bone marrow transplantation and other causes.

Platelets

Platelets are indicated for treatment of patients with active bleeding due to severe thrombocytopenia (low platelet count) caused by decreased platelet production (for example, leukaemia) or increased platelet consumption. Platelets can be indicated in two clinical settings: when there is thrombocytopenia with bleeding or likely bleeding, or when there is an abnormality of platelet function with bleeding or likely bleeding.

Low platelet count can result from either of two main causes:

reduced and inadequate production of platelets by the patient’s bone marrow; or

normal production of platelets coupled with increased destruction of platelets by the patient’s circulation.

Abnormal platelet function can be inherited or acquired. The latter genesis is the more common and can be induced by certain medications, including aspirin. There is also a condition of the bone marrow, more common in the elderly, whereby the production of blood cells, including platelets, is both inefficient and disordered—myelodysplastic syndromes (National Blood Authority, Undated – a).

Fresh Frozen Plasma

Fresh frozen plasma (FFP) is also called plasma for transfusion or clinical fresh frozen plasma. It is plasma separated from whole blood and frozen within 18 hours. Its use is indicated for patients with a coagulopathy who are bleeding, or at risk of bleeding, where specific therapy (such as vitamin K or factor concentrate) is not appropriate or available. FFP may be used in massive transfusion, cardiac bypass, liver disease or acute DIC (disseminated intravascular coagulation) to replace labile coagulation factors. It may be indicated to correct warfarin overdose with life threatening bleeding in addition to Prothrombin Complex Concentrates (PCC; vitamin K dependent factor concentrates). FFP may be indicated for Thrombotic Thrombocytopenic Purpura (TTP).

Intravenous immunoglobulin

Intravenous immunoglobulin (IVIg) is an immunoglobulin preparation suitable for intravenous use. It can be used for replacing Immunoglobulin in both inherited and acquired immune deficiencies, modulate immunological/antibody mediated diseases (autoimmune diseases), either acutely (for example, thrombocytopenia) or chronically (for example, chronic inflammatory demyelinating polyneuropathy, CIDP):

replace immunoglobulins in a number of inherited primary immune deficiency conditions;

treat acute and chronic autoimmune diseases; and

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treat rare or debilitating mainly neurological and immunological conditions.

In Australia, IVIg is used to treat more than 90 conditions, the vast majority of which fall within the three disciplines of haematology, immunology and neurology. Neurological use is the single main indication.

Albumin

Albumin 20 per cent is indicated, mainly, in the management of critically ill patients with extremely low albumin or burns. Albumin 4 per cent is indicated, mainly, in the management of shock associated with significant hypoalbuminaemia, for fluids maintenance, therapeutic plasmapheresis and for ‘pump priming’ in cardiothoracic surgery (Australian Red Cross Blood Service, 2009).

Prothrombinex‐VF

Prothrombinex‐VF (PTX) is a clotting factor concentrate which contains clotting factors II, IX and X, and some other agents. Historically, there was a modest use of Prothrombinex‐VF concentrate for haemophilia patients with inhibitors. This use has now been largely replaced by the use of rFVIIa and Factor Eight Inhibitor bypass Agent (FEIBA) therapy. The principal use in Australia is now for warfarin reversal.

Source: NBA Monograph Series 05 Whole Blood and Red Cell Products Draft Version 1 NBA Monograph Series 08 Albumin Draft Version 1 NBA Monograph Series 07 Fresh Frozen Plasma Draft Version 1 NBA Monograph Series 06 Platelets Draft Version 1 NBA Monograph Series 2010 Prothrombinex-VF Version 1

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Project Methodology Sapere Research Group was contracted to undertake two blood sector related projects, namely Analysis of Cost Drivers and Trends in the Blood Sector and Options to Manage Appropriate Use of Blood and Blood Products. Except for the reporting stage, the two projects were undertaken in concert. Information and data gathering, including a literature review and consultations with key stakeholders, were undertaken to serve the purposes of both projects.

The projects were conducted by the same multidisciplinary project team. The team comprised expertise in health policy, financial and economic analysis, and public sector governance, as well as extensive knowledge in the clinical and managements aspects of the Australian blood sector. The team also contained extensive international experience of blood sector management and practice.

The main body of work of the projects was conducted over the period from July 2010 to March 2011. Literature and other information sources referenced within this report were current during that time period. In broad terms, the main steps in the conduct of the projects were to:

obtain project inception briefings from the project management team and senior personnel in the Department of Health and Ageing (DOHA);

agree to a detailed project plan with DOHA;

gather information and data;

conduct consultations;

analyse all project information;

design and construct a model for forecasting blood usage;

prepare project reports.

The main sources of information for the project were:

an extensive literature review;

information and data sourced from key organisations in the Australian blood sector;

consultations with key stakeholders.

In addition, the project team received advice from a Blood Projects Reference Group. The Reference Group was chaired by DOHA and comprised members from:

National Blood Authority (NBA);

the Blood Service;

nominated Jurisdictional Blood Committee (JBC) members (the representative from Queensland represented the larger States and South Australia the smaller jurisdictions).

The Reference Group’s role was to provide advice and information to the project team throughout the course of the projects. The Reference Group participants are provided in Appendix 2.

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LITERATURE REVIEW

The literature review included material provided by the NBA, the Blood Service and DOHA. Some of the material was provided in confidence. Other literature, data and information were sourced from the public domain, including peer reviewed medical and scientific journals (principally from MEDLINE/PUBMED) and reviews and information available through the World Wide Web. MEDLINE covers over 20 million records of articles published in thousands of international journals in the fields of medicine and health. As a complementary interface for searching MEDLINE, PubMed (http://www.pubmed.gov) was chosen as the tool for our literature research on the given topics.

The MEDLINE/PubMed search found no peer reviewed medical and scientific journal articles specifically on ‘Price Signals and Appropriate Use’ and ‘Blood Costs and Trends’. Searches were conducted on the basis of other key words to lead to relevant material.

A search of literature and information from sources other than MEDLINE was undertaken to identify reputable sources of information relevant to the two projects.

In general, the literature search results obtained for allogeneic (fresh) blood products showed a strong focus in Australia and overseas over the last decade or so on patient blood management and the costs and patient (adverse) impacts rather than a focus on the administration of the products.

The results obtained from searching the ‘grey’11 literature also indicated a very strong focus in Australia over the last decade or so on patient blood management and the costs and patient (adverse) impacts rather than a focus on the administration of the products. In addition, the literature provided significant data and information on appropriate use, costs, trends, and pricing (including price signalling) for blood products (including plasma derived and recombinant products). The ‘grey’ literature also included many links to other relevant literature, data and information.

DATA

The majority of data were sourced from:

NBA;

the Blood Service;

Australian Bureau of Statistics (ABS);

DOHA.

Other data sources included the health authorities in each of the states and territories, and NSW CEC, and also Medicare Australia.

In addition, much data were sourced from the literature discovered through the literature review.

A list of data collected during the course of the review is at Appendix 3.

CONSULTATIONS

Consultations with key stakeholders were undertaken to:

11 “Grey” literature refers to reports and articles not appearing in peer reviewed journals.

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inform analysis through the gathering of information, data and importantly ideas based on the knowledge and experience of stakeholders;

refine and/or to test options developed through the projects.

Consultation for the two blood projects was targeted and involved organisations and individual experts in the Australian blood sector. Group meetings, interviews and teleconferences were used to conduct the consultations. The choice of means took into account the availability of individuals and timing considerations. Not all individuals contacted were available within the timeframe of the projects. Some key stakeholders presented alternative contacts for the team to consult. Some contacts that were unavailable to speak to were offered the opportunity to provide written comments.

Consultations were conducted in two stages.

The first stage primarily involved the general gathering of information, thoughts and ideas relevant to the aims and scope of the two projects. The information collected through this first stage of consultation was analysed along with data and other inputs into the two projects.

Stage 1 consultations were conducted over the period from late August to mid October 2010.

A second stage of targeted consultation sought additional information, for example, for the refinement of options. Second stage consultations also tested options with a select number of key organisations or individuals.

Stage 2 consultations were conducted in concert with the drafting of the reports.

Consultation was targeted. Nevertheless, the range and number of stakeholders consulted was large. The terms of reference for the project stipulated that the following key stakeholders be consulted:

NBA;

the Blood Service;

DOHA;

JBC;

NHMRC; and

other stakeholders as mutually agreed by the DOHA, as required and at the contractor’s discretion.

Organisations and persons consulted included State and Australian Government officials involved in the management and regulation of the blood sector, clinicians and professional colleges, blood product suppliers, pathology representatives, and health consumer/patient group representatives.

A full list of persons consulted is at Appendix 4.

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Overview of Australian System This section provides an overview of arrangements for the administration of the blood and blood product sector in Australia. It covers the governance structure of the Australian blood sector, recent government reviews of the sector, the national blood supply system, legislation, stakeholders and funding.

GOVERNANCE OF THE AUSTRALIAN BLOOD SECTOR

A Review of the Australian Blood Banking and Plasma Product Sector, chaired by the Rt Hon Sir Ninian Stephen, reported in March 2001. The major recommendations of the report were adoption of a national partnership approach between the Australian Government and the states and territories with an intergovernmental agreement giving effect to the proposed changes and the establishment of the National Blood Authority to undertake national supply planning and management of blood and blood products for Australia.

Following the Stephen Review, the Australian Government and the states and territories signed the National Blood Agreement in February 2003, which sets out a coordinated national approach to policy setting, governance and management for the Australian blood sector.

Governments agreed that the national approach should have the following key features:

(a) national agreement on the objectives of Governments for the Australian blood sector;

(b) a primary policy setting and governance role for Australian Government, State and Territory health Ministers, supported by a JBC of senior officials;

(c) a National Blood Authority (NBA), to manage the national blood supply;

(d) joint funding of the national blood supply by the Australian Government and the states and territories; and

(e) a nationally agreed framework for the management of safety and quality issues within the Australian blood sector.

The primary policy objectives for the Australian blood sector set out in the Agreement are:

(a) to provide an adequate, safe, secure and affordable supply of blood products, blood related products and blood related services in Australia; and

(b) to promote safe, high quality management and use of blood products, blood related products and blood related services in Australia.

In pursuing the primary policy objectives, the Agreement notes the Parties will have regard to a number of secondary policy aims. Among other things, these include:

(a) meeting international obligations and standards;

(b) maintaining reliance on voluntary, non‐remunerated donations of whole blood and plasma;

(c) promoting national self‐sufficiency;

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(d) providing products to patients free of charge and based on clinical need and appropriate clinical practice;

(e) promoting optimal safety and quality in the supply, management and use of products, including through uniform national standards.

The Agreement allocates key responsibilities to the Australian Health Ministers’ Council (AHMC) including:

(a) the general oversight of the Australian blood sector;

(b) the determination of national policy;

(c) the oversight of coordination, cooperation and information exchange between bodies with safety and quality or national supply roles within the Australian blood sector;

(d) the oversight of the implementation of the Agreement.

The AHMC is also responsible for issuing policy principles to the NBA through the Commonwealth Minister in accordance with the NBA legislation. The AHMAC, a standing committee of senior officials, supports the AHMC.

The National Blood Authority (NBA) is an Australian Government statutory agency, established under the National Blood Authority Act 2003 to improve and enhance the management of the Australian blood and plasma product sector at a national level. The NBA represents the interests of the Australian, State and Territory governments and sits within the Australian Government’s Health and Ageing portfolio. It is subject to the Financial Management and Accountability Act 1997, Auditor General Act 1997 and the Public Service Act 1999.

The NBA manages the national planning and purchasing of blood in close co‐operation with other stakeholders. Each year it is required to coordinate and produce, for approval by all Health Ministers, a National Product Price List and National Supply Plan and Budget for blood and blood products. It also negotiates and manages contracts on behalf of all states and territories, and the Australian government with suppliers of blood and blood products to enable the development of an agreed single national pricing schedule.

The NBA is jointly funded by all governments with the Australian Government contributing 63 per cent and the States 37 per cent.

The JBC is responsible for all jurisdictional issues relating to the national blood supply, including policy, demand, supply planning and product distribution, budgeting and evidence‐based approaches to emerging products, services and technologies. It provides advice and support to the AHMC through the Clinical, Technical and Ethical Principal Committee (CTEPC) and the AHMAC.

The JBC is also responsible for considering advice from, and providing advice to, the NBA, on matters related to the national blood supply and overseeing the NBA’s role in relation to blood supply contracts. All Australian, State and Territory governments are represented on the JBC, which is the conduit between governments and the NBA.

CTEPC was established in 2006 to provide advice to the AHMAC on a range of issues in relation to clinical, technical and medico‐ethical issues that affect the formulation of health care policy or delivery of health care services across multiple jurisdictions. It is responsible for eight subcommittees including the JBC.

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The Therapeutic Goods Administration (TGA) was established under the Therapeutic Goods Act 1989. The TGA carries out a range of assessment and monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard with the aim of ensuring that the Australian community has access, within a reasonable time, to therapeutic advances. Among other things, it is responsible for regulating all blood, blood components and plasma derivatives supplied in Australia and for auditing supplies against good manufacturing practice.

A summary of the governance structure of the Australian blood sector is set out below.

FIGURE 14: GOVERNANCE STRUCTURE OF THE AUSTRALIAN BLOOD SECTOR

Source: National Blood Authority Australia – Annual Report 2009-10

RECENT REVIEWS OF THE NATIONAL BLOOD ARRANGEMENTS

ADMINISTRATIVE REVIEW OF THE NATIONAL BLOOD ARRANGEMENTS 2009 (THE WEBSTER REPORT)

In 2009 an administrative review was undertaken, focusing on governance issues and implementation of the 2003 National Blood Agreement. The Review established that the 2003 arrangements, especially through their move to a national approach, have been a major improvement on the previous fragmented and inconsistent arrangements across the country. The Review concluded that radical changes to the Arrangements were not needed at this time.

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However the Review proposed an increased strategic policy development role for the CTEPC of AHMAC. Among other things, this would include:

taking the lead role in advancing strategic policy initiatives from AHMC and AHMAC and in advising AHMC/AHMAC of emerging policy issues and options;

providing a formal problem solving and dispute resolution function for matters referred by the JBC;

assisting the JBC and the NBA to develop a three year strategic plan, taking account of government initiatives in the broader health sector;

convening a consultative forum, including the NBA and representatives of the Blood Service, CSL, other suppliers, consumer groups, hospitals and clinicians.

The JBC would continue to maintain a lead role in operational matters, including reviewing and submitting National Supply Plans and Budgets. The NBA should work with JBC and CTEPC to identify three‐year priorities.

The Review concluded a multi‐year supply planning and budgeting process should be introduced with plans covering a four‐year timeframe, updated each year.

The Review also suggested a number of projects be undertaken, particularly in the areas of funding, sustainability and improved management of blood product use under the Agreement.

It is understood the conclusions in the report have been accepted.

REVIEW OF AUSTRALIA’S PLASMA FRACTIONATION ARRANGEMENTS (THE FLOOD REVIEW)

Australia’s plasma fractionation arrangements were reviewed in 2006 at the request of the then Minister for Health and Ageing by an independent committee chaired by Mr Philip Flood AO. The review was in line with commitments under the Australia‐United States Free Trade Agreement. The Review recommended that overseas fractionation of Australian plasma was not an advantageous option for Australia. It further recommended that urgent action must be taken to increase plasma collection rates in view of prospective shortfalls in domestic supply collected by the Blood Service. Plasma products should be imported to address any shortfall. In March 2007 the Australian Government announced that the current arrangements whereby Australian plasma is processed in Australia would continue.

NATIONAL BLOOD SUPPLY SYSTEM

ROLES OF GOVERNMENT

Part 3 of the National Blood Agreement contains administrative arrangements for the national blood supply. It covers the establishment of the NBA as the manager of the national blood supply and specific roles for the AHMC, JBC, NBA and states and territories in the national blood supply.

The AHMC approves national supply and production planning and budgeting proposals from the NBA.

Together with the Australian Government, the states and territories are responsible for:

establishing the policy framework and specific policies relating to the national blood supply;

overseeing the NBA’s management of the blood supply arrangements;

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fostering the development and implementation of best‐practice systems to promote efficient use and minimal wastage of blood and blood related products;

providing information on demand for blood and blood related products;

managing local issues.

The JBC refers national blood supply change proposals for evidence‐based evaluation, participates in the supply planning and budgeting process and assists in oversight of the NBA’s role in management of the national blood supply.

The main functions of the NBA in relation to the blood supply system are to:

gather information from State and Territory health authorities and other relevant organisations in relation to the demand for blood and blood products;

develop, on a consultative basis, an annual supply plan and budget;

negotiate and administer contracts for the collection, production and distribution of blood and blood products;

develop the national price list for products, based on the annual supply plan and budget and on the contracts with suppliers.

SUPPLIERS OF BLOOD AND BLOOD PRODUCTS

To implement the annual National Supply Plan, the NBA has supply contracts with the following suppliers of blood and blood related products, which it manages closely to ensure that demand for product is always met:

The Australian Red Cross Blood Service (the Blood Service)

The Blood Service, a Division of the Australian Red Cross Society, collects fresh blood from voluntary donors in order to produce a variety of blood components. The Blood Service also collects plasma, which is provided to CSL Ltd for fractionation into a variety of products that are then purchased through the NBA contract with CSL. The Blood Service then distributes the blood components to hospitals.

The NBA manages the relationship with the Blood Service—the sole supplier of fresh blood‐related products in Australia—and is responsible for negotiating and managing the Blood Service Deed of Agreement.

The Agreement is structured around the Blood Service meeting state and territory requirements for the supply of blood, blood products and associated services. Under the Agreement, the Blood Service collects, manufactures and distributes fresh blood products (also known as blood components) from voluntary donations. It also distributes plasma products and a number of imported blood products to hospitals and other end users in Australia. The Agreement brings together the needs of the Australian Government and the state and territory governments in a single, national Agreement with the Blood Service.

The Australian Government provides 63 per cent of the funding for the Blood Service and the State and Territory Governments’ combined contribution is 37 per cent.

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CSL Limited

Most plasma‐derived products used in Australia are manufactured by CSL Limited from plasma collected by the Blood Service under the CSL Australian Fractionation Agreement. Materials for blood diagnostic purposes and some imported products are also sourced through CSL.

Other Pharmaceutical Companies

In 2009‐10, the NBA held contracts for the provision of blood and blood related products under standing offer arrangements with:

CSL Limited, Octapharma Australia Pty Ltd and Lateral Grifols Pty Ltd for the provision of overseas‐sourced IVIg;

Baxter Healthcare Pty Ltd, Wyeth Australia Pty Ltd and Novo Nordisk Pharmaceuticals Pty Ltd, for the provision of a range of imported plasma‐derived and recombinant blood products;

CSL Limited, Lateral Grifols Pty Ltd, Ortho‐Clinical Diagnostics Inc (USA) and Abacus ALS (formerly Australian Laboratory Services), for the supply of diagnostic reagents.

Australia is totally reliant on an imported supply of plasma derived Factor XI and Factor XIII, anti‐inhibitor coagulant complex concentrates, Protein C and a plasma‐derived Rh(D) immunoglobulin product. These products are either not economical to manufacture in Australia or, as is the case for IVIg, the Australian system is unable to produce enough product to meet demand. IVIg is accordingly imported as a contingency to supplement domestic supply under a Standing Offer.

Table 2 below shows the value of blood and blood related products, purchased by supplier, in 2008‐09 and 2009‐10.

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TABLE 2: BLOOD AND BLOOD RELATED PRODUCTS PURCHASED, BY SUPPLIER, 2008‐09 AND 2009‐10

Supplier Products Purchased 2008–09

($million)

2009–10

($million)

CSL Ltd Plasma Products

albumin products

immunoglobulin products (including

IVIg and hyperimmune products)

plasma‐derived clotting factors

Diagnostic reagent products

blood grouping sera

reagent red cell products

Imported Blood Products

Factors XI and XIII

IVIg standing offer

Management of National Reserve

162.09 186.16

Australian Red Cross Blood Service Fresh Blood Products

whole blood

red blood cells

platelets

clinical fresh frozen plasma

cryoprecipitate

plasma for fractionation

432.62 456.12

Baxter Healthcare Pty Ltd Imported Blood Products

Recombinant Factor VIII

Protein C

Factor VII concentrate

Factor Eight Inhibitor Bypass Agent

(FEIBA)

WinRho

84.09 90.62

Wyeth Australia Pty Ltd Imported Blood Products

Recombinant Factor VIII

Recombinant Factor IX

48.65 48.94

Novo Nordisk Pharmaceuticals Pty Ltd Imported Blood Products 17.40 26.42

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Supplier Products Purchased 2008–09

($million)

2009–10

($million)

Recombinant Factor VIIa

Octapharma Pty Ltd Imported Blood Products

IVIg Standing Offer

46.90 48.69

Lateral Grifols Pty Ltd (formerly

DiaMed Australia Pty Ltd)

Diagnostic Reagent Products

blood grouping sera


0.92 0.81

Ortho‐Clinical Diagnostics (Johnson &

Johnson Company)

Diagnostic Reagent Products

blood grouping sera


0.47 0.43

Abacus ALS Pty Ltd Diagnostic Reagent Products

blood grouping sera


0.04 0.04

TOTAL 793.18 858.23 Source: National Blood Authority Australia – Annual Report 2009-10

In relation to the above table, Lateral Grifols also have a standing offer for supply of IVIg with the NBA. Its primary purpose was to allow jurisdictions to buy product outside the NBA arrangements but NBA bought minor quantities for particular patients. In October 2011 Octapharma recalled Octagam and the NBA currently uses the Lateral Grifols contract to supply imported IVIg product for Australia.

SUPPLY PLANNING PROCESS AND BLOOD SUPPLY CHAIN

As indicated above, each year the NBA is required to coordinate and produce a National Product Price List and National Supply Plan and Budget for blood and blood products for approval by the Australian Health Ministers’ Conference. Supply planning commences twelve months prior to the next supply year and must be endorsed by the JBC, and AHMC to allow continued funding of blood and blood products to suppliers of blood and blood products. In addition, the NBA is responsible for the intensive management of products in short supply.

The NBA prepares initial Supply Plan estimates on the basis of information from the states and territories. This takes into account factors such as historical trends, policy decisions and predicted hospital workloads over the forward period. It then consults with the Blood Service on its ability to collect the blood and plasma for fractionation volumes required in the draft Plan. It also consults with other suppliers on their ability to provide the blood products required. Estimates are provided to each jurisdiction for consideration and sign off before final approval by the JBC and the AHMC.

The blood supply chain and payment flows from suppliers to end‐users are described in Figure 15 on the following page.

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FIGURE 15: BLOOD SUPPLY CHAIN


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The NBA is responsible for establishing blood and blood products supply Deeds (or Contracts), including for the imported recombinant products, with suppliers. The contracts provide for supply of products to the State and Territory health providers.

The Blood Service is the sole organisation in Australia responsible for collecting whole blood and blood components. All donations of blood are from voluntary and non‐remunerated donors. Blood is collected either as whole blood, or through a process called apheresis, which can isolate and extract blood components, that is plasma and platelets.

The Blood Service is also the sole manufacturer of fresh blood products in Australia. From whole blood, the Blood Service produces a range of products, which fall into several main categories, namely:

red cells (suspended);

platelets;

FFP;

plasma for fractionation.

Plasma for fractionation is supplied free of charge to CSL Ltd for further processing into specific blood products. The main categories of plasma derived blood products are:

immunoglobulins;

hyperimmune products;

clotting factors.

The NBA negotiates contracts with other pharmaceutical companies for the supply of plasma‐derived and recombinant blood products. These include Abacus ALS, Baxter Healthcare Pty Ltd, Lateral Grifols Pty Ltd, Novo Nordisk Pharmaceuticals Pty Ltd, Octapharma Australia Pty Ltd, Ortho‐Clinical Diagnostics Inc (USA) and Wyeth Australia Pty Ltd.

Contracts specify agreed products, supply and delivery arrangements, performance criteria and product prices. The Blood Service is required to deliver fresh blood products and plasma derived products manufactured by CSL to Approved Health Providers (AHPs). AHPs are almost all public and private hospitals. However, some blood products are delivered outside of hospital settings, for example, home deliveries for haemophilia treatment and some anti Rh(D) immunoglobulin are supplied to some recipients such as fertility and family planning clinics outside the hospital environment. Supply contracts with other pharmaceutical companies require delivery on the basis of orders from Approved Recipients (ARs) in accordance with the contract or as otherwise determined by the NBA under the contract.

There are jurisdictional differences in relation to inventory management of blood and blood products, but, typically, blood and blood products are receipted and held by a hospital’s internal blood bank or pathology unit (mostly for public hospitals), or another storage facility. For example, some private hospitals use off‐site pathology laboratories to store their blood and blood products.

The product is released for use by the Pathology Unit, under request by the treating clinician. Different hospitals have different procedures for release of product. Release of IVIg and Recombinant Factor VIIa (rFVIIa) require approval by the Blood Service against indicated uses before release for use.

The internal arrangements within hospitals for the issue and use of blood and blood products vary widely. State and Territory guidelines emphasise that it is important during all stages of the supply process that appropriate documentation is obtained. It is a requirement of the National Association of

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Testing Authorities (NATA) that laboratories record the fate of every fresh unit transfused with name, UR number, date of birth and probably location for look back purposes to identify any viral transmission. The clinical record of the hospital cannot be searched, as the donation number might be recorded but not really searchable. Units of blood are commonly searched for through pathology systems. However, data and information on exactly what happens with blood and blood products within hospitals are not routinely collated.

Before release from pathology for clinical use, fresh blood components are grouped to ensure blood type and Rh(D) compatibility with the recipient. Red cells are also cross matched with the prospective recipient. A single unit of red cells may be grouped and even cross matched many times without release, as the blood may not ultimately be required for use in a certain procedure. Increasingly, pathology performs the less expensive function of group match and hold, and completes the full cross match only if the blood is required to be released.

In the private setting, prescription of blood or blood products for transfusion by a clinician is eligible for a Medicare Benefits Schedule (MBS) rebate item, as are the pathology functions associated with the dispensing of blood and blood products.

LEGISLATION, GUIDELINES AND STANDARDS

The collection, storage, use and disclosure of information relating to blood and blood products are regulated by a mixture of legislation, guidelines and standards. These include:

the legislative framework for the protection of information and health privacy based on the Privacy Act 1988 and similar state and territory legislation;

State and Territory Human Tissue Acts, which regulate aspects of the removal of human tissue, including blood donations, as well as blood transfusions. Among other things, the legislation covers requirements for the consent to removal of blood;

the NHMRC/ASBT Blood Components guidelines;

standards and guidelines released by the National Pathology Accreditation Advisory Council (NPAAC), which apply to pathology laboratories accredited in Australia. Laboratories that want to claim Medicare benefits must be accredited by the NATA to the appropriate standard. Laboratories can bill patients directly and avoid Medicare and NATA if desired;

AHMC Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) in Australia (2008);

state and territory government health authority policies and guidelines which typically set out the obligations of a health care facility to ensure the safe and appropriate use of blood and blood products. The guidelines cover the obligations of clinicians (medical practitioners and nurses) for safe and effective transfusion therapy, transfusion verification procedures and transfusion equipment, hospital transfusion service staff for transportation, storage, inventory management

and labelling and health service managers for reporting of infections and retention of records.

STAKEHOLDERS

The roles of Australian Government, state and territory governments have been described above in relation to the governance structure for the Australian blood sector and the supply planning process. The key roles of the NBA and other government agencies such as the TGA have been covered as well as the major suppliers of blood including the Blood Service, CSL Ltd and other pharmaceutical companies.

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Other key stakeholders include a wide range of professional bodies representing doctors generally such as the Royal College of Physicians of Australasia (RACP), or specialist clinicians and scientists working in the blood sector such as the Australasian Society of Thrombosis and Haemostasis (ASTH) and Australian Haemophilia Centre Directors Organisation (AHCDO). There are some umbrella bodies representing a range of separate professional organisations. The Pathology Associations Council (PAC) brings together representatives of the various national organisations that are involved in pathology service delivery, with a particular emphasis on professional issues such as workforce, training, professional development, quality and safety. PAC aims to present a single voice to State and Federal governments on issues relating to pathology.1213

Other groups of medical and other specialists working in the blood sector are represented through peak professional bodies such as the Royal College of Pathologists of Australasia (RCPA), the Australia and New Zealand Intensive Care Society (ANZICS), the Health Informatics Society of Australia Ltd (HISA), the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT), the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Haematology Society of Australia and New Zealand (HSANZ). These organisations are primarily interested in training and support for their members, promotion of research, quality and safety issues and advocacy to governments.

Pathology practices are represented by the Australian Association of Pathology Practices (AAPP) which is the national peak body for private pathology in Australia covering both small specialized laboratories as well as large corporations with laboratories nationwide. AAPP aims to provide high quality, affordable, safe and accessible pathology services. Public pathology services are represented through the National Coalition of Public Pathology (NCOPP), which advocates advancing public pathology with the public, the medical profession and governments.

Other stakeholders include:

hospitals and area health services;

professional workers in the blood sector such as clinicians, pathologists, haematologists, researchers and nurses and associated unions such as the Australian Nursing Federation;

the NHMRC;

universities and medical research institutions;

those working for the various State Emergency Medical Retrieval Services;

health insurance companies who have strong interests in patient outcomes and costs.

Finally blood users also have a significant stake in Australia’s blood system. Some are represented through organisations such as the Haemophilia Foundation Australia (HFA), which represents people with haemophilia, von Willebrand disorder, and other related inherited bleeding disorders, and their families. HFA is committed to improving treatment and care through representation and advocacy,

13 Professional societies or associations covered by the PAC include the Australasian Association of Clinical Biochemists (AACB), Australian Institute of Medical Scientists (AIMS), Australian Society of Cytology (ASC), Australian Society of Clinical Immunology and Allergy (ASCIA), Australian Society for Microbiology (ASM), Australian and New Zealand Society of Blood Transfusion (ANZSBT), Endocrine Society of Australia (ESA) and Human Genetics Society of Australasia (HGSA)

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education and the promotion of research. Immune Deficiency Foundation of Australia (IDFA) supports children, teenagers and adults with primary immune deficiency disorders.

FUNDING

Australia’s blood sector is government funded with cost‐shared arrangements between the Australian, State and Territory governments. In general State and Territory governments contribute 37 per cent and the Australian Government 63 per cent. Funds provided to the NBA are used to purchase and manage blood, blood products and services from the Blood Service, CSL Limited and pharmaceutical companies as well as operational costs of the NBA.

In NSW and Tasmania, State Health authorities then pass this cost down to the Area Health Service level, and in some instances at least in Tasmania, further passed down to individual hospitals. In Tasmania, the apportionment is done on the basis of historical use, that is the percentage of the hospital’s total use for the previous year.

Providers bill the NBA, on a monthly basis, for the volume of blood issues they deliver. On the basis of these invoices, NBA bills the Australian Government for 63 per cent and each State for 37 per cent of the cost.

The total cost of supply of blood and blood related products over the period 2003‐04 to 2009‐10 and for the operation of the NBA over the same period are shown in Table 3 and Table 4 respectively.

TABLE 3: PRODUCT SUPPLY COST(a) FOR BLOOD AND BLOOD RELATED PRODUCTS(b), 2003–04 TO 2009–10

Year Amount ($million) Growth

2003–04 442.3 –

2004–05 492.6 11 %

2005–06 544.5 11 %

2006–07 615.2 13 %

2007–08 678.8 10 %

2008–09 771.4 14 %

2009–10 850.9 10 %

Average over period 12 %

Source: National Supply Plan and Budget, 2003-04 to 2009-10, National Blood Authority

(a) The ‘product supply cost’ refers to the cost to governments for the purchase of blood and blood products only. It does not include additional costs such as administrative expenses of health authorities and the NBA or the cost of the National Managed Fund.

(b) Excluding diagnostic blood products.

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TABLE 4: GOVERNMENT FUNDING FOR THE OPERATION OF THE NBA, 2003–04 TO 2009–10

Year Amount ($million) Growth (per cent)

2003–04 7.4 –

2004–05 8.4 12.7

2005–06 10.4 24.1

2006–07 10.1 ‐2.6

2007–08 9.6 ‐4.8

2008–09 9.2 ‐4.9

2009–10 8.9 ‐3.3


APPROVAL PROCESSES

Under the National Blood Agreement, interested parties can make proposals for changes to products or services on the National Products and Supply List. Schedule 4 of the National Blood Agreement provides for evidence‐based evaluation, information and advice to be provided to support decisions on these changes.

The NBA’s Multi‐Criteria Analysis (MCA) Framework has been agreed by officials as the primary tool to assess applications in the following circumstances:

changes to products currently supplied under the National Blood Arrangements; or

proposed additions to the National Product and Services List (NPSL) of new blood products or services.

An assessment under the MCA framework can involve one or two cycles, depending on the complexity of the evaluation and information supplied. The Framework has been designed to ensure that assessment of new products or services addresses the primary and secondary policy objectives of the National Blood Agreement, as well as broader government policy objectives.

The objective of the first cycle is to identify whether there is sufficient evidence to support a change to blood products or services funded under the National Blood Arrangements. Following Cycle 1, if the JBC considers that further analysis or information is needed, this will be undertaken in Cycle 2.

New products cannot be submitted for listing on the NPSL unless they are registered with the TGA for supply in Australia.

The NPSL does not list specific products but rather a generic description of a product category. Just because a product is on the list, does not mean that government is committed to buy any particular quantity of the product at any particular time, nor are governments committed to any particular brand of a product. A decision to purchase a product is always subject to additional processes after completion of the MCA assessment.

The MCA framework applies to both ‘within category’ and ‘outside category’ change proposals.

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‘Within category’ proposals are defined as changes to products already approved by Health Ministers and which are already listed on the NPSL. A ‘within category’ change will be assessed by the NBA against the MCA Framework. A decision on whether to approve or not approve the change would usually be made by either the NBA or the JBC. In general, the NBA is able to approve the change if the MCA assessment shows that the change is either positive or neutral against all criteria. If the change is not neutral or positive against all of the MCA criteria, the proposal must be forwarded to the JBC for consideration. The JBC will assess the application and either approve/reject the proposal or require further analysis of the proposal via Cycle 2.

An ‘outside category’ proposal is a proposal for:

a new product/service not already on the approved NPSL; or

a change to a product on the NPSL that has altered the nature of that product to take it outside the definition of the listed product.

Examples may include:

a new recombinant product;

different route of administration;

change in active ingredients; and

an imported product, where the current category definition only includes product manufactured from Australian plasma.

All ‘outside category’ proposals are considered as Schedule 4 applications and must be considered by the JBC (Figure 16). JBC has three options:

if there is sufficient information to make a decision, and the proposal is considered to be non‐material (for example does not have a material effect on clinical care outcomes, production, supply or cost under the national blood supply), JBC can reject or approve the proposal;

if there is sufficient information to make a decision, and the proposal is considered to be material (for example does have a material effect on clinical care outcomes, production, supply or cost under the national blood supply) JBC must refer the matter to AHMC for decision;

if there is insufficient information to make a decision, then JBC can require further information for a more detailed Cycle 2 analysis.

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FIGURE 16: ASSESSMENT PROCESS PATHWAY

*Subject to any relevant procurement/contract provisions

Source: National Blood Authority

ACHIEVEMENTS IN THE AUSTRALIAN BLOOD SECTOR

In the 1990s the world blood sector was undergoing change in response to a number of pressures, predominantly around cost and safety issues. In response to this, a number of countries undertook reviews of the organisation and management of their blood programs, leading to significant reorganisation and structural reforms. These reforms were based on rationalisation, consolidation and integration, as well as clarification of roles and responsibilities and system‐wide approaches to achieving improved management, accountability and performance as part of risk management.

In Australia, the 1995 McKay Wells Review (McKay, 1995), recommended the formation of the Blood Service as a national blood service (rather than individual State‐based services) providing the impetus for structural change. This, together with the establishment of the AHMAC Blood and Blood Products Standing Committee, provided the first steps towards a national approach to managing Australia’s blood sector.

The McKay Wells Review was followed in 2001 by the Review of the Australian Blood Banking and Plasma Product Sector, chaired by Sir Ninian Stephen (2001), as mentioned previously. The Stephen’s review had identified a number of shortcomings in the system, including that it was:

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fragmented and administratively costly and inefficient being driven by suppliers rather than clinical demand;

lacking transparent evidence‐based assessment mechanisms for new products and technologies;

providing disincentives to achieving national economies of scale; and

subject to rising cost pressures from the dynamic, changing nature of the blood sector.

NBA was established as a consequence, to address these shortcomings.

In an exceptionally short time and as an excellent example of cooperation between state and territory governments and the Australian Government, all parties accepted the recommendations of the Stephen Review, and the National Blood Agreement was signed by all Australian governments.

As indicated earlier, the National Blood Agreement also sets out the primary and secondary policy objectives of all governments in relation to the Australian blood sector. Major policy aims are the safe, secure, adequate and affordable supply of blood and blood products in Australia; and the highest quality, effectiveness and efficiency for the Australian blood sector. Supporting principles include a continued policy of national self‐sufficiency in blood and blood products; voluntary, unpaid donations of blood and plasma; and the supply of such products free of charge to patients, based on clinical needs and appropriate clinical practice.

The role of the Australian Health Ministers’ Conference and establishment of the JBC are also set out in the National Blood Agreement. The Australian Health Ministers’ Conference is charged with a number of functions, including general oversight and determination of national policy for the Australian blood sector, and oversight of the implementation of the National Blood Agreement. As was indicated earlier, the JBC’s roles include providing advice to, and dealing with less significant issues under the authority of, the Australian Health Ministers’ Conference.

The JBC also has responsibilities in relation to the national blood supply. These include:

referring proposed changes to the national blood supply to appropriate bodies for evidence‐based evaluation;

participating in the development of NBA supply and production planning and budgeting;

considering advice from and advising the NBA on matters related to the national blood supply;

monitoring developments in safety and quality; and

overseeing the NBA’s role in relation to contracts.

The roles of the state and territory governments are aimed at better use of blood and blood products.

Together, the NBA Act and the National Blood Agreement form the foundations of the current arrangements within the Australian blood sector and the major achievements in the blood sector have been made through the NBA under its Act and the National Blood Agreement.

During 2003–04 (National Blood Authority, 2004) the NBA’s key priorities were focused, by necessity, on putting in place adequate operational infrastructure and identifying and minimising risks that might otherwise have prevented the supply system from responding in a crisis.

The mission set by the NBA in its establishment year was “To build a new national platform to achieve (our) vision while meeting current blood supply needs.” In that year the NBA fulfilled its primary function of meeting current blood supply needs. The refinement of the 2003–04 National Supply Plan

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and Budget and the development of new ones for 2004–05 on behalf of the Australian Health Ministers’ Conference were particularly taxing tasks for the NBA, as governments had to base their demand estimates on unreliable past consumption data and had limited capacity to influence demand once their budgets had been set.

The NBA’s stocktake of achievements after the first five years of operation was impressive. The challenges in the first year were considerable — not the least being the task of creating an organisation from scratch and tackling the expectations arising from the National Blood Agreement. Other challenges for the NBA included:

developing and managing new relationships at a national level;

building confidence in the clinical and scientific communities about the roles and responsibilities of the new authority;

demonstrating value for governments early in its existence.

Today, the NBA negotiates and manages contracts covering all the blood and blood‐related products used in Australia. It also has a broad international network, coordinates a national approach to blood supply, usage and conservation, manages a diversity of stakeholder relationships, and has recently started work to drive improvements in transfusion appropriateness and blood sector performance analysis.

MAJOR NATIONAL ACHIEVEMENTS—2003‐04 TO 2008‐09

In the first five years of its operation the NBA:

improved contract management, delivering significant cost savings to all Australian governments;

implemented a diverse and innovative range of supply contingency provisions that have prevented significant stock shortages;

established clear governance decision‐making frameworks that integrate blood into the overall decision‐making framework for health sector risk planning;

built highly effective relationships with key stakeholders;

delivered a range of safety and quality initiatives such as the recent Initial Australian Haemovigilance Report (2008) and the Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) in Australia (2008);

began data collections on product issues and usage to assist in developing policies relating to appropriate use of products, and a rigorous analysis of future supply and demand; and

implemented a range of strategies to reduce inappropriate use of blood products.

The achievements of the first five years of the NBA shown in Table 5 have been possible because of a commitment by the NBA to six principles, namely:

detailed analysis of costs, options, international comparators and stakeholder concerns;

meticulous planning of resources and activities against clear goals;

seeking creative and innovative ways to achieve better outcomes;

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a high‐level of stakeholder involvement and communication, both in the planning and designing phases, as well as implementation;

careful management of cautious implementation;

regular monitoring and review for all the projects undertaken.

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TABLE 5: FIVE YEARS OF AUSTRALIAN BLOOD SECTOR ACHIEVEMENTS, 2003–08

National Blood Authority Act

Obligations

Achievement Outcome

To provide assistance:

in accordance with national

blood arrangements to a

committee referred to in those

arrangements

to the Board

to the advisory committees (if

any) established under section

38.

Provided secretariat services to 53 JBC

meetings.

JBC focus evolved from strong

operational concerns to strategic

developmental focus.

Board directly engaged in informing

strategic advice to the General Manager.

Clinical Advisory Council established to

provide detailed clinical advice and was

instrumental in the development of the

blood counts program.

Effective governance

framework that supports

consolidated policy

decision‐making and

implementation across all

jurisdictions.

To carry out national blood arrangements relating to annual plans and budgets for the production and supply of blood products and services.

National supply plan process created and implemented on an annual basis.

Presentation of plans delivered progressively earlier to Ministers each year.

Suppliers advised of indicative volumes more than six months before the commencement of plan.

Mid‐year reviews designed and implemented on a regular basis from 2004.

Verification procedures for ordering and receipting negotiated and implemented.

Suppliers provided with improved certainty and clarity of government supply requirements.

An improved level of accountability in blood expenditure.

To enter and manage contracts and

arrangements for the collection,

production and distribution of the

blood products and services

necessary to ensure a sufficient

supply of blood products and

services in all the states and covered

territories.

New Deed with ARCBS negotiated and signed.

New Deed with CSL Ltd negotiated and signed.

New contractual arrangements for diagnostics implemented.

New Standing Order arrangements for the importation and implementation of IVIg.

New Deeds for imported plasma and recombinant products negotiated and signed.

No stock‐out of any

product in five years.

Substantial savings

achieved.

Improved shelf life of some

products.

Improved product access

for patients.

Improved products and

product range.

To carry out national blood

arrangements to ensure that there

is a sufficient supply of blood

products and services in all the

states and covered territories.

Effective management of the development of:

Factor VIII and Factor IX Guidelines

(2006)

Criteria for the Clinical Use of Intravenous

Immunoglobulin (IVIg) in Australia (2008).

Guidelines on the prophylactic use on

RhD immunoglobulin (anti‐D) in

High‐quality, evidence‐

based guidelines for high

cost products developed in

consultation with the

clinical community and

published.

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Obligations

Achievement Outcome

obstetrics (2004).

Biostate shortage contingent supply

management.


arrangements relating to:

(a) Safety and quality measures.

ARCBS requests to governments for

funding for increased levels of

leucodepletion, bacterial contamination

and sample archiving assessed.

Rolled out recombinant FVIII for all

patients seeking this product.

Obtained funding for ARCBS to

implement TGA requirement for changes

to Hb tests.

Blood standard requirements integrated

into hospital accreditation reform.

Product recipients have

access to a selection of

some of the world’s best

products.

Government approved 100

per cent leucodepletion

and 100 per cent bacterial

contamination testing of

platelets.

(b) Contingency measures and risk

mitigation measures for the supply

of blood products and services.

Agreed National Blood Supply

Contingency Plan.

Risk mitigation strategies incorporated

into plasma and recombinant products

contracts.

New management arrangements for

National Managed Fund instigated.

In‐country reserve requirements.

Effective coordination of

national management of

blood product shortages.

Blood sector integrated

into health contingency

planning.

Hierarchy of risk response

options.

To liaise with and gather information from governments, suppliers and others about matters relating to blood products and services.

Ongoing horizon scanning project implemented.

Fresh Blood Products: Production Benchmarking and Demand Drivers released.

Strategic workshops initiated for JBC.

Created Blood Suppliers Forum, Professional and Community Forum and the Clinical Advisory Council.

Engaged stakeholders in specific projects, for example ABDR redevelopment, NIMS and product tender processes.

Established Haemovigilance project working group.

Established an Expert Working Group to manage the review of guidelines for use of fresh blood components.

All contracts and major projects informed by international research, government, clinical and community needs.

To provide information and advice

to the Minister and the Ministerial

Council about matters relating to

blood products and services.

Approximately 20 papers have been

submitted to AHMC for ministerial

approval.

Recommended position on barcoding

policy for blood products.

Ministers provided with

consolidated strategic

national policy and funding

advice.

Ministers provided with

P a g e | 29


Obligations

Achievement Outcome

accurate and timely advice.


arrangements relating to the

funding of the supply of blood

products and services, and the

NBA’s operations.

Established the NBA with independent infrastructure and services, including: IT systems; outsourcing of noncore business systems; appropriate and best practice governance arrangements; and key policies and processes to support the operation of the NBA.

Maintained an active recruitment program to address new functions.

Implemented an NBA Fellows program to ensure the NBA has access to high‐quality advice.

Implemented Clinical Advisory Council to ensure the NBA has access to high level clinical advice to guide policy and program development.

Recognition as high performing agency through:

Prime Minister’s Silver Award for

Excellence in Public Sector

Management and

Comcover Award for Excellence in

Risk Initiatives. Highly Commended

in the category of Risk Initiative.

NBA recognised for public

service excellence.

NBA recognised for high

quality risk management

procedures.

Ensure that funding and supply

contracts for the national blood

supply include appropriate

obligations on suppliers to meet

safety and quality standards and to

enforce those obligations.

All contracts comply with this

requirement.

Requirement for additional pathogen

inactivation steps in some CSL Ltd

products in new Plasma Products

Agreement.

Co‐ordinated supply response for

implementation of variant‐Creutzfeldt‐

Jakob disease mitigation steps.

Australian supply contracts

provide some of the

world’s best products.

Maintain a systematic approach to

identify new developments and to

provide a clearinghouse and

coordination function for

information in relation to new

developments.

Framework for assessment of new

technologies established.

Supply contracts to provide information

on new and emerging issues.

Blood Sector Data Strategy.

Framework to ensure that

the sector is informed and

well poised for timely

responses to new and

emerging pressures.

Standardised approach to

information management

and data systems

development in the blood

sector to be implemented.

P a g e | 30


Obligations

Achievement Outcome

Facilitate coordination, integration,

cooperation and information

exchange between the NBA and

other bodies with a safety and

quality role in the Australian blood

sector, and between those other

bodies.

Coordinated blood sector input to

National Safety and Quality in Healthcare

Commission accreditation reforms.

Provided input to the Information

Strategy for the National Safety and

Quality in Healthcare Commission.

Designed ABDR with input from National

E‐Health Transition Authority.

Red Cell Utilisation Workshop sharing

data between states.

Co‐sponsored support for market

research on red cell prescribing

behaviours of doctors (with NSW

Government).

Blood issues integrated

into health S&Q reform

agenda.

Provide information and advice to

the JBC and to the Ministerial

Council (through the JBC).

Provided information on new and

emerging products, technologies and

procedures to JBC on a regular basis.

Established strategic workshops for JBC.

Prepared more than 500 papers to JBC.

Sound coverage and

management of

operational issues.

Policy directions to be

informed by careful

consideration of emerging

information.

Act on behalf of the JBC to purchase

and organise activities under

Clauses 34 (a), (b) and (c).

Started distribution review.

Established a better practice fund to

develop local ideas to national

application.

Four projects commenced

under this fund.

Facilitate the development of

national information systems for

safety and quality issues in relation

to the Australian blood sector.

Haemovigilance reporting design

requirements.

Australia’s first Haemovigilance report to

guide sector reform.

ABDR redevelopment to provide

improved demand data.

Awareness of transfusion‐

related reactions

increased.

Australia now meets best

international practice in

Haemovigilance.

High‐quality, evidence‐

based guidelines for high

cost products developed in

consultation with the

clinical community and

published.

Source: National Blood Authority Annual Report 2007-08. October 2008.

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FIGURE 17: NATIONAL BLOOD AUTHORITY – FIRST FIVE YEARS HIGHLIGHTS

Source: National Blood Authority Annual Report 2007-08. October 2008

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Since this major look back at achievements in the Australian blood sector significant improvement continues. The recent major achievements in the Australian blood sector are set out below in brief.

MAJOR NATIONAL ACHIEVEMENTS SINCE 2008‐09 (NATIONAL BLOOD AUTHORITY, 2009)

Management and implementation of planning, funding and risk‐management activities

Achievements have included:

development of the National Supply Plan and Budget (NSPB) bringing together the best understanding of current and future demand and supply trends. Endorsement by Australian Government, and state and territory health ministers of the 2008–09 NSPB ensured the continued supply of a range of products required to meet clinical need. Expenditure on the blood supply was $789.9 million, which was 2.3 per cent less than the Commonwealth Budget estimate of $808.7 million (National Blood Authority, 2009). Most importantly, the NBA was able to ensure that products were available at all times to meet clinical need;

the then Parliamentary Secretary, Senator the Hon Jan McLucas, launched the National Blood Supply Contingency Plan in November 2008. This plan establishes a clear decision‐making framework for managing the blood supply in cases of supply shortage or demand surges and integrates with broader health emergency management arrangements. The plan was successfully activated from 22 August to 23 October during a shortage of red cells. Actions taken under the plan resulted in clinical practice not being compromised during this period:

three other incidents—the Victorian bushfires, the Ashmore Reef incident and the pandemic (H1N1) 2009 outbreak— had the potential to result in inadequate supply. While none of these incidents required activation of the National Blood Supply Contingency Plan, the NBA worked with governments and suppliers to closely monitor the supply situation;

understanding future risks—as well as opportunities—is a core activity within the NBA. Its horizon‐scanning program continues to deliver early warning of possible future pressures and opportunities. In 2008–09 the NBA upgraded its reporting in the area;

the NBA established a meeting of international colleagues under the banner of the collaboration of National Plasma Products Supply Planners to exchange information and data on planning and risk‐management activities.

Enhanced data capture and analysis

Improvement in the blood sector, in both supply chain management and clinical practice, is hampered by a lack of data and analysis. Along with jurisdictions and suppliers, the NBA is taking steps to redress this shortfall.

In 2008–09 the NBA, on behalf of all governments, launched the redeveloped ABDR to provide to stakeholders information about patients with haemophilia and other bleeding disorders. The registry also allows for more reliable supply forecasting and planning.

The NBA internal data warehouse capability also improved greatly with the rollout of the IDMS, which will assist in the further development of the National Supply Plan and Budget and the transition to multi‐year budgeting and demand and supply planning.

The release of the first Blood Measures Guide by the NBA was a world first in establishing a nationally accepted set of measures on the use and effectiveness of fresh blood components. It

P a g e | 33

is hoped that over time greater consistency in measurement will enable meaningful comparison of research results and lead to a better understanding of the use of fresh blood components.

Sector improvement projects

Progress on a number of projects continued to identify opportunities to improve the sector, especially in relation to value for money. In 2008–09 this included the following:

development of a multi‐criteria analysis framework for assessing new products or services (Schedule 4 of the National Blood Agreement) that aligns blood sector assessment methodology with that used in the Medical Benefits Scheme and the Pharmaceutical Benefits Scheme (PBS) and quantifies consideration of each of the objectives of the National Blood Agreement;

completion of the first phase of the review of distribution arrangements for plasma and recombinant blood products;

organisation of the National Blood Sector Conference on 6‐7 November 2008. The successful conference focused on the identification of barriers to wider adoption of best practice in blood management and alternative therapies.

Supply of blood and blood products

The NBA continues to place a high emphasis on being knowledgeable about the international blood sector, so that it can take a highly informed approach to development of the best‐value contracts to deliver the blood products Australia needs. In 2008–09 their contract‐management and negotiation activities made a key contribution to minimising increases in the overall cost and affordability of the blood supply for governments. Among the highlights were:

prices for plasma and recombinant products were effectively restrained. NBA analyses demonstrate that during the past six years the collective effect of its activities is that there have been no increases in prices, despite global price rises;

three contracts for imported plasma and recombinant products were successfully negotiated, with savings;

all ministerial recommendations of the Blood Service business study progressed according to the agreed timetable, 32 per cent being fully implemented. This includes agreement to move towards a three‐year rolling planning cycle and establishment of an output‐based funding model;

new contractual arrangements are in place with the Blood Service from 1 July 2009;

the NBA progressed approvals through governments for the Blood Service’s new principal blood manufacturing sites in accordance with the time frames necessitated by the Blood Service’s project plans. This included managing the independent assessment of the Victoria and Tasmania principal site for the Australian Health Ministers Conference.

Monitoring and implementing the appropriate and safe use of products

Improving product and patient safety is a crucial element of the National Blood Agreement, and good progress in this regard was achieved in a number of projects during 2008–09. Highlights included:

information on adverse effects from blood transfusions has been increased through the establishment of the ongoing Australian National Haemovigilance Program. Among other things,

P a g e | 34

this involved finalising the definitions of the national minimum Haemovigilance data sets and developing a methodology for assessing the capability of jurisdictions to provide the required data;

the revised NHMRC’s guidelines for fresh blood will provide the most contemporary evidence‐based information on when and how to use fresh blood components. In 2008–09, under the guidance of an expert working group of 27 clinicians, we began an extensive review of international research into blood‐related guidelines. Evidence reports and associated recommendations for critical bleeding and peri‐operative guidelines are due early 2010;

the availability and quality of education on blood administration have been improved through the establishment of a national framework for the continued development of the South Australian e‐learning project;

information on where red cells are used has been improved as a result of the development of a draft minimum data set to guide further red cell use data‐linkage activities.

In 2009‐10 the NBA:

won the 2010 United Nations Public Service Award in the category of Advancing Knowledge Management in Government;

signed a new agreement with CSL Limited to maintain a safe, secure and affordable supply of domestically produced blood plasma products;

won the Comcover Award for Excellence in Risk Management;

implemented a pilot project for a national electronic Order and Receipting Blood System;

completed a public consultation of the critical bleeding module on the PBM guideline designed to assist in the management of patients with life threatening bleeding;

agreed to output based funding principles with the Blood Service, and a 12‐month extension of the current Deed;

developed a Stewardship statement for use of blood and blood products by Approved Health Providers;

commenced review of the Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) in Australia (2008);

improved data capture and analysis to provide greater insight on the management, administration and use of blood and blood products;

completed Stage 2 of the review of distribution arrangements of plasma and recombinant products;

published the second Australian Haemovigilance Report 2010, which aims to increase the sector’s understanding of transfusion related adverse events.

The NBA has always believed that developing and maintaining the organisational capability to do its work well was a top priority, including having access to high‐quality information so that it can be a well‐informed purchaser and program manager. To that end, over the last six years the NBA has built a very effective private and civil network that provides it with the information it needs to maintain a high standard of work. It was therefore a very exciting day for NBA in June 2010 when the NBA’s

P a g e | 35

work in this area was recognised by it winning the 2010 United Nations Public Service Award in the knowledge management category.

OTHER ACHIEVEMENTS IN 2009–10

Supply of blood and blood products

Among the NBA’s key functions are the development and management of the National Supply Plan and Budget and the management of contracts for blood and blood related products. In 2009–10, governments spent $872.8 million on blood and blood related products which are supplied free of charge to Australian patients (National Blood Authority, 2010a).

In 2009–10 current contracts with major suppliers CSL Limited and the Blood Service both expired. The NBA put a great deal of effort into negotiating the successful renewal of the contracts. In December 2009 a new agreement with CSL Limited was signed. Subject to a review in 2014, the agreement will run until 31 December 2017. Over that period this will ensure a secure supply of plasma products and services and provide improved value for money for governments.

Other major achievements in this area included:

successfully ensuring that blood products were available at all times to meet clinical need;

reaching agreement with the Australian Red Cross Society and the Blood Service on the principles of an output based funding model, to be implemented from 1 July 2010, and on the extension of the current Deed of Agreement for a further year;

reaching agreement with Octapharma to extend the existing contract for the supply of imported IVIg until December 2011, with improved value for money;

extending the contracts for diagnostic reagent products until June 2011;

completing the 2010–11 National Supply Plan and Budget with a higher level of jurisdictional engagement on clinical demand than in previous years. The plan was approved by the JBC in December 2009 and received ministerial approval in April 2010; and

achieving savings to governments of $22 million, compared to the prices that governments would have otherwise incurred before the establishment of the NBA.

Risk and sector improvement

The NBA continues to give high priority to its obligation to manage blood sector risks, especially those related to supply security. It does this by ensuring that responsibility and accountability lie with those best placed to manage risk. There were several highlights in this area during 2009‐10:

the NBA was awarded the 2009 Australian Government Comcover Award for Excellence in Risk Management for the National Blood Supply Contingency Plan;

an annex to the National Blood Supply Contingency Plan, dealing with the management of transfusion‐transmitted infections in the blood supply, was drafted;

agreement was reached with the Blood Service on the need to standardise stock holdings for fresh blood components to assist in identifying appropriate trigger points for the National Blood Supply Contingency Plan and enabling improved reporting.

The NBA restructured its organisation in 2009 to enhance its capacity to capture and analyse data and provide insight into the management, administration and use of blood and blood products. NBA

P a g e | 36

reported significant progress during 2009‐10 on data capture that will allow the NBA to deliver more robust and accurate reports to jurisdictions on product use, the balance between supply and demand throughout the year, and intensive management of products in short supply where this is necessary.

Other projects are currently at various stages of progression within the NBA to improve the overall efficiency of the sector. These include:

development, for national application, of an electronic ordering and receipting blood system for use by blood banks in ordering products from suppliers and enhancement of the system for additional data capture;

review of the distribution of plasma and recombinant products;

KPMG business review of the Blood Service;

Development of Statements on National Stewardship Expectations for health providers of blood and blood products and of Expectations for the Blood Service 2010–11 to 2012–13.

SAFETY OF SUPPLY

In terms of the safety record of the sector, Australia appears to fare no worse than other countries. This was the conclusion of the 2010 report of the HAC (2010). That report noted that a number of OECD countries have national haemovigilance programs, and that some publish annual reports about the number and types of adverse events occurring in their hospitals. The 2010 HAC report concluded “there is no evidence at this stage to suggest that the rate of transfusion errors in Australia is outside the range experienced in OECD countries.” (Ibid.) The report indicated that “(i)n common with other OECD countries, such as the United Kingdom, New Zealand, Sweden and Canada, the risks to the safety of transfused patients in Australia were predominantly in the hospital environment, arising from procedural errors.” (Ibid.) For example, the 2008 report of the HAC had indicated that approximately 65 per cent of incidents reported in Australia had involved procedural errors and that this was “broadly compatible with (the results from) other OECD countries.” (Ibid.) For example, the UK Serious Hazards Of Transfusion Annual Report 2008 (Serious Hazards of Transfusion, 2008) indicated that procedural errors represented 59 per cent of cumulative numbers of cases reviewed in the period 1996‐2008.

ACHIEVEMENTS IN PROMOTING APPROPRIATE USE OF BLOOD AND BLOOD PRODUCTS

There have been a number of achievements in this area through the efforts of the NBA as well as states and territories. These achievements are discussed in the accompanying report Options to Manage Appropriate Use of Blood and Blood Products (Sapere Research Group 2011 unpublished).

P a g e | 37

Use of Blood and Blood Products The aim of this section of the report is to present a description and analysis of various aspects of current and recent historical trends in blood use in Australia.

DATA CONSIDERATIONS

The description of blood use in Australia in this section of the report is based on data relating to issues of blood and blood products.

There can be a difference between volumes of products issued and volumes actually used, particularly for fresh blood products which experience varying rates of discard due mainly to expiry. Consistent data on the volumes of actual use of blood and blood products by health providers were not found for this report. Similarly, consistent data on wastage rates was not available. Wastage figures for fresh blood products are collected by the Blood Service under a voluntary system—the ERIC database. Participation in ERIC currently covers between 70 – 80 per cent of all fresh blood issues nationally, with differing intensities of participation among the jurisdictions14. It was therefore not possible to derive accurate figures for the actual volume of blood and blood product use.

In general, payments for blood and blood products are based on the delivery of product to health providers. Hence data on product issues (as opposed to actual use) were readily available. Given that all blood supplied in the system, whether used or not, is paid for by governments under current arrangements, the volume of blood and blood products issued is nevertheless pertinent to the analysis in this report. Volume of ‘issue’ is hence mostly used synonymously with volume of ‘use’ throughout this report.

The analysis of blood usage volumes in this report is based principally on the National Supply Plan and Budget as provided by NBA. Unless otherwise indicated in the report, volume and cost figures relate to actual volumes and costs over the period 2003‐04 to 2009‐10. Future modelling of demand incorporated National Supply Plan and Budget projections for the period 2010‐11 to 2014‐15.

References in the text, tables and figures to ‘units’ of fresh blood products, unless otherwise indicated, refer to standard units as indicated in Table 6.

14 In 2009‐10, approximately 75 per cent of red cell, 78 per cent of platelet and 72 per cent of FFP issues were reported on in ERIC. Queensland, SA, WA, Tasmania and Victoria all reported on 100 per cent (or very close to it) of their fresh blood issues in ERIC.

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TABLE 6: STANDARD UNITS FOR FRESH BLOOD PRODUCTS

Fresh Product Category Standard unit

Whole Blood 405‐495mL

Red Cells 200mL leucodepleted or equivalent

Platelets 160mL or equivalent

FFP 295mL

Cryoprecipitate 30‐40mL

Cryo‐Depleted Plasma (CDP) 165mL

Other (mixed)

Plasma for Fractionation (PfF) Kg

Source: NBA National Supply Plan and Budget

No data were available to the project to ascertain the breakdown in blood and blood product volumes between the public and private sectors. However, hospital separations data were used as an indicator of relativities in this regard.

Data on hospital separations were sourced from the National Admitted Patient Care Collection, 2003‐04 to 2008‐09 held by the DOHA. These data were analysed as presented, that is, in the absence of any advice to the contrary, it was assumed that any coding accuracy was of an acceptable standard.

To analyse trends in the use of blood and blood products in this report, products are generally grouped as follows:

Fresh blood products (also known as blood components), with emphasis on:

red cells;

platelets;

FFP.

Plasma derived products, with emphasis on:

intravenous immunoglobulin (IVIg);

albumin;

Prothrombinex‐VF.

Recombinant products, with emphasis on:

Recombinant Factor VIII (rFVIII);

Recombinant Factor VIIa (rFVIIa).

P a g e | 39

OVERVIEW OF BLOOD USE IN AUSTRALIA

In general, the absolute volumes of blood and blood products issued have been increasing over recent years15, and increases in costs have followed.

The number of hospital separations involving transfusion has been growing as a proportion of all hospital separations.

Some distinct, general patterns in usage rates emerge from the data:

the rates of growth in volume differ markedly among individual products:

: for example, growth in red cells has been quite stable over the period 2003‐04 to 2009‐10, at an average annual rate of around 1.3 per cent. Over the same period, IVIg use has grown by an average 12 per cent per annum, and Prothrombinex‐VF by an average 29 per cent per annum;

rates of growth on a per population basis differ markedly between the fresh product and plasma derived groups:

: the use rate of fresh blood products has been quite flat. On the other hand, plasma derived products have grown strongly;

there are significant differences in use patterns among the states and territories for individual products. For example:

issues of red cells, the most voluminous fresh blood product, have maintained strong relative differences for a number of years between states and territories. The highest rate of use per 1000 population in 2009‐10 was recorded by SA at 43.97 units. NSW recorded the lowest rate among the large states with 34.80 units. WA and Tasmania recorded just over 30 units per 1000 population;

: Victoria’s use of Prothrombinex‐VF outstrips all other states and territories. It records the highest absolute volume of Prothrombinex‐VF issues, more than double that of New South Wales or Queensland, despite its population size;

: the use of IVIg in Queensland has grown very rapidly since 2003‐04:

hospital separations data suggest that this growth may be attributable mainly to the private sector;

significant jurisdictional differences are evident also in the rate of change in transfused hospital separations as a proportion of total separations:

: with some jurisdictions, notably NSW and ACT, moving against the national trend by showing a decline in the proportion of transfused separations over 2003‐04 to 2008‐09;

15 An exception is whole blood, the use of which has declined in favour of use of blood components (red cells, platelets etc).

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use of blood and blood products is influenced by demographic factors, with older age groups tending to be higher users of fresh and, most likely, the major plasma derived products (particularly IVIg and Prothrombinex‐VF);

while there were no direct data distinguishing public and private usage volumes, hospital separations data show that the public sector accounted for 68 per cent of transfused separations, and the private sector 32 per cent in 2008‐09:

the ratio differed per jurisdiction. In Queensland, the proportion accounted for by the private sector was around 50 per cent, much higher than the national average.

WHAT DRIVES DEMAND FOR BLOOD IN AUSTRALIA?

A range of factors influence the demand for blood and blood products. They include the following:

demographic factors;

rates and incidence of disease;

clinical guidelines and indicated uses for products;

clinician prescribing practices;

treatment technologies and techniques;

policy decisions and programs, such as blood management initiatives;

wastage;

inappropriate use of blood and blood products.

DEMOGRAPHIC FACTORS

As will be discussed in more detail below, an ageing population is correlated with higher demand for blood and blood products. Blood and blood products are used in surgery and in the treatment of cancers and other conditions. As is the general trend in the health sector, health conditions associated with the use of blood and blood products occur to a greater extent among the elderly.

RATES AND INCIDENCE OF DISEASE

Demand for blood shifts with the burden of disease. Different blood products are indicated for different conditions. Their rates of demand move in response to changes in the incidence of these conditions. This will be discussed further below, where the main clinical uses of blood and blood products are examined.

CLINICAL GUIDELINES, INDICATED USES AND OTHER RULES OF USE

Clinical guidelines generally guide the prescription of blood and blood products. Changes to the range of indicated uses have an obvious impact on demand.

Additional ‘rules’ or procedures can influence demand, including, for example, authorisation regimes for the release of products for use as in the case of IVIg. The case of IVIg is an example of a national system of ‘gatekeeping’ on use. Local arrangements can also apply, such as administrative request forms. Another procedure that can affect demand for blood is patient consent.

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CLINICAL PRACTICE

Ultimately it is the clinician who decides how much blood a patient will receive for a given indication. Clinical practice is of course guided by clinical guidelines, but in Australia, the extent of the influence of guidelines is not great. This will be discussed the section on best practice below.

In addition, not all blood and blood products in Australia are covered by active guidelines, and the guidelines that do exist in some instances are much generalised.

Clinicians are influenced by a range of other factors. Stakeholders consulted during the course of the project highlighted the factors below. Based on anecdotal evidence and opinions of stakeholders only, these influences might be arranged in the following descending order of influence:

Patient outcomes—clinicians are driven by the interests of their patients’ wellbeing. What they believe is good for their patients, however, is influenced in turn by some of the factors appearing below.

Peer practice—stakeholders, including clinicians themselves and other health care professionals, emphasised that clinicians are influenced very strongly by the practice of their peers. Clinicians view their peers as other clinicians within their area of specialty.

Prescribing ‘culture’—this often pertains to individual institutions. There is much evidence indicating wide variations in prescribing practice from hospital to hospital. Some stakeholders referred to the prescribing culture arising from the practices of senior clinicians within institutions. Because junior clinicians are trained and mentored by these senior clinicians, prescribing norms perpetuate.

Education and training—clinicians base practice on their formal education, but also vocational training. Many stakeholders expressed the view that formal education of the clinical use of blood could be improved. Appropriate practice needed to be included in vocational training, but that should capture not just registrars, but senior clinicians as well, for the reasons indicated under the discussion of prescribing culture above.

Knowledge and evidence—stakeholders agreed that the knowledge and evidence base was an influence over clinical practice, with the following qualifications. Knowledge and evidence had to be accessible, and many clinicians struggle to stay abreast of new knowledge and evidence. The fact that blood and blood products are used by clinicians across many specialties, who are not themselves specialists in blood clinical practice, makes the dissemination of new knowledge and evidence an even greater challenge in the blood sector. Stakeholders felt that the practice of peers was a much stronger influence over behaviour.

Financial incentives—some stakeholders questioned whether financial incentives were an influence on prescribing behaviour. In particular, stakeholders pointed to the MBS item 13706 which provides for a Medicare Benefit to be paid in respect of the charge a clinician can make for the administration of blood in a private health care setting. The project team could find no conclusive evidence in relation to this:

: Figure 18 below shows the pattern of use of the MBS item by jurisdiction. The rate of use in Queensland stands out. However, as will be seen later in this report, this pattern of use of the item is supported by a high rate of private sector separations involving transfusion relative to other jurisdictions (Usage Patterns Indicated by Hospital Separations, p.75);

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: some stakeholders relayed anecdotes of ‘prescription splitting’ in some private hospitals, for example, instead of prescribing a two‐unit dosage of red cells; the clinician would split this into two by one unit prescriptions. If this occurred, the clinician would be able to charge a Medicare‐claimable fee for each prescription;

o the project team has no evidence as to whether this practice occurs. It is also unclear whether the practice would influence the demand for blood and blood products;

o the remuneration arrangement (perhaps ironically) could encourage compliance with one aspect of the NHMRC/ASBT Blood Components guidelines, namely, to prescribe blood one unit at a time to enable progressive assessment of the patient. As will be indicated later in this report, common practice in Australia is to prescribe multiple units at a time;

o on the other hand, Medicare item 13706 could encourage clinicians to over‐prescribe blood.

FIGURE 18: MBS ITEM 13706 NUMBER OF SERVICES PER 100,000 POPULATION, 1994‐95 TO 2009‐10

*Population base is Medicare registered population.

Source: http://www.medicareaustralia.gov.au/about/stats/

TREATMENT TECHNIQUES & TECHNOLOGY

Changes in this area could influence the demand for blood positively and negatively. Upward pressure on the blood budget would be influenced by:

development of new blood products;

development of surgical treatments for conditions not previously operable.

0

5000

10000

15000

20000

25000

30000

35000

Number of services per 100,000 population*

ACT

Average

NSW

NT

QLD

SA

TAS

VIC

WA

P a g e | 43

Downward pressure would be influenced by:

Development of development of substitute therapies for existing blood products;

Wider application of blood saving surgical techniques, such as laparoscopic treatments.

POLICY DECISIONS AND POLICY INITIATIVES

Policy decisions can act to expand or contract demand. An example of a policy decision, which expanded costs to budget, was the introduction of universal leucodepletion of red cells. On the other hand, policy initiatives can act to reduce demand for blood. An example would be the introduction of usage authorisation or other ‘gatekeeping’ procedures to govern the release of products for use. The introduction of PBM initiatives has also shown an impact on reducing demand for blood and blood products. This is indicated to a limited degree in the section on best practice below. It is taken up in more detail in the accompanying report on Options to Manage Appropriate Use of Blood and Blood Products (Sapere Research Group 2011 unpublished).

WASTAGE

Wastage acts to inflate demand for blood and blood products. Time series data on wastage rates in the sector in Australia were difficult to obtain. Hospitals participate on a voluntary basis in a database system held by the Blood Service, known as ERIC, which records wastage rates for the main fresh blood products. Some States have achieved 100 per cent participation over the last few years (namely Queensland, Victoria, Tasmania, SA and WA), while the coverage in the other jurisdictions remained poor in 2009‐10 (Table 7).

The ERIC fresh blood product wastage figures for 2009‐10 show varying levels of waste in the sector among the jurisdictions (Figure 19 and Table 7). However, there is a degree of consistency in the rates of red cell wastage among those five jurisdictions, which reported on 100 per cent of their red cell issue. The exception was WA, where red cell wastage was markedly lower in 2009‐10. Wastage rates for platelets and FFP were also lower in WA. This trend might be influenced by the high degree of concentration of hospital activity in the State in Perth.

It is reasonable to expect that there will always be a degree of wastage involved in the management of such products with short shelf lives. The challenge is particularly difficult in the case of regional and remote health facilities, where timely distribution of product is more difficult. The wastage levels in NT may reflect this.

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FIGURE 19: FRESH BLOOD PRODUCT WASTAGE: DISCARDED PRODUCT AS A PROPORTION OF PRODUCT ISSUED TO PARTICIPANT HOSPITALS (a), BY STATE AND TERRITORY, 2009‐10

Source: ERIC Wastage Data from ARCBS Trends and Analysis Report 2009-10

(a)Figures are derived from the ARCBS ERIC database and represent the volume of product discarded as a proportion of total product issued to hospitals in the jurisdiction, which participated in ERIC reporting in 2009‐10. For example, 175 units of red cells were discarded by the single hospital in the ACT, which reported in ERIC in 2009‐10. This represented 12 per cent of the total red cell issues to that single hospital in that year.

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

ACT NSW NT QLD SA TAS Total VIC WA

Fresh Frozen Plasma

Platelets

Red Cells

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TABLE 7: ERIC WASTAGE DATA 2009‐2010

Component Family

Data ACT NSW NT QLD SA TAS VIC WA Total

Red Cells Total Quantity Supplied 12,727 250,066 5,100 170,125 72,064 15,174 209,213 69,233 803,702

Quantity Supplied to Hospitals Registered in ERIC 1,459 71,736 1,403 169,845 71,630 15,174 202,099 66,340 599,686

Quantity Returned by Hospitals Registered in ERIC 1 18 2 116 49 15 159 15 375

Loss Reported by ERIC 175 3,438 372 10,328 4,172 959 11,448 1,293 32,185

Per cent of Waste 12.00 % 4.80 % 26.60 % 6.10 % 5.80 % 6.30 % 5.70 % 1.90 % 5.40 %

Per cent of ERIC Participation 11.50 % 28.70 % 27.50 % 99.80 % 99.40 % 100.00 % 96.60 % 95.80 % 74.60 %

Platelets Total Quantity Supplied 2,071 35,425 908 36,074 9,720 2,834 35,819 9,016 131,867

Quantity Supplied to Hospitals Registered in ERIC 10 10,036 192 36,064 9,711 2,834 35,311 8,982 103,140


Loss Reported by ERIC 1,465 144 7,054 1,455 616 9,343 68 20,145

Per cent of Waste 0.00 % 14.60 % 75.40 % 19.60 % 15.00 % 21.80 % 26.50 % 0.80 % 19.60 %


FFP Total Quantity Supplied 2,234 58,566 593 38,614 14,659 1,514 33,456 12,874 162,510

Quantity Supplied to Hospitals Registered in ERIC 102 15,393 110 38,604 14,659 1,514 32,991 12,770 116,143


Loss Reported by ERIC 10 1,955 52 5,262 1,099 221 3,660 216 12,475

Per cent of Waste 9.80 % 12.70 % 47.30 % 13.70 % 7.50 % 14.60 % 11.10 % 1.70 % 10.70 %


Source: ARCBS Trends and Analysis Report 2009-10

Note: ‘Per cent of ERIC participation’ refers to the proportion of total red blood cell issues to the State or Territory which are captured by reporting in ERIC.

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INAPPROPRIATE USE

Inappropriate use of blood and blood products resulting in overuse, acts to artificially inflate the level of demand. Efforts to promote more appropriate use will necessarily assist in containing demand, and hence, cost pressures, without compromising patient outcomes. This is taken up in more detail later in this report.

FRESH BLOOD PRODUCTS

Fresh blood products principally comprise red cells, platelets and FFP.

Red cells resuspended are the most widely used fresh blood product. They are given to increase the oxygen carrying capacity of the blood, for example, in patients with severe anaemia following major blood loss after trauma and surgery. Red cells are also used in elective settings to treat patients with severe anaemia—for example, patients with severe anaemia secondary to chronic disease, in the setting of chemotherapy and bone marrow transplantation and other causes.

Leucodepleted red cells have a shelf life of up to 42 days.

Platelets are indicated for treatment of patients with active bleeding due to severe thrombocytopenia (low platelet count) caused by decreased platelet production (for example, leukaemia) or increased platelet consumption. Platelets can be indicated in two clinical settings: when there is thrombocytopenia with bleeding or likely bleeding, or when there is an abnormality of platelet function with bleeding or likely bleeding.

Low platelet count can result from either of two main causes:

reduced and inadequate production of platelets by the patient’s bone marrow, (this aspect is not part of this review) or;

normal production of platelets coupled with increased destruction of platelets by the patient’s circulation.

Abnormal platelet function can be inherited or acquired. The latter genesis is the more common and can be induced by certain medications, including aspirin. There is also a condition of the bone marrow, more common in the elderly, whereby the production of blood cells, including platelets, is both inefficient and disordered—myelodysplastic syndromes (National Blood Authority, Undated – a).

Platelets have a shelf life of just 5 days.

FFP is plasma separated from whole blood and frozen within 18 hours. Its use is indicated for patients with a coagulopathy who are bleeding, or at risk of bleeding, where specific therapy (such as vitamin K or factor concentrate) is not appropriate or available. FFP may be used in massive transfusion, cardiac bypass, liver disease or acute DIC to replace labile coagulation factors. It may be indicated to correct warfarin16 overdose with life threatening

16 Warfarin is the most widely used oral anticoagulation agent in the world. It is prescribed to patients who have suffered a thrombosis or who are at significant risk of thrombosis. Examples are deep venous thrombosis and pulmonary embolism. There is a growing demographic of patients for whom warfarin therapy is currently indicated including patients with prosthetic heart valves, with a history of recurrent thrombosis, past catastrophic thrombosis, with certain inherited disorders where there is a strong disposition to thrombosis, with malignancies at risk of thrombosis, a variety of other

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bleeding in addition to PCC (vitamin K dependent factor concentrates). FFP may be indicated for TTP.

FFP has a shelf life of up to 12 months.

Whole blood was once an important fresh blood product in terms of volume, but its use has declined dramatically in recent years in favour of the use of the blood components described above. The use of blood components is not only safer in most cases, but also enables the release of plasma from the whole blood collected for the production of other specialised blood products.

Plasma for fractionation is another important fresh blood product. Its volume has been growing strongly. Plasma for fractionation is an intermediate product, used in the production of fractionated, or plasma derived, products. Hence its demand is a derived demand. Trends in the volume of use of plasma for fractionation will not be separately examined in this section. Rather, the trends for the finished, plasma derived products will receive focus.

Currently, in Australia, national volumes of fresh blood products stand at the levels indicated in Table 8.

TABLE 8: VOLUMES OF FRESH BLOOD PRODUCTS, 2009‐10

Product/Group Volume (Standard units)(a) Volume per 1000 population

Whole Blood Products 18 0.00

Red Cell Products 795,892 36.39

Platelet Products 128,492 5.88

Clinical Fresh Frozen Plasma 160,813 7.35

Cryoprecipitate Products 64,734 2.96

Cryo‐depleted Plasma 11,872 0.54

Other Fresh Products 8,377 0.38

Plasma for Fractionation 451,000 20.62

(a) See Table 6 Source: NBA National Supply Plan and Budget, actual volumes, ABS catalogue 3101.0 – Australian Demographic Statistics.

The highest use individual products within the major product categories are as follows:

red cells—leucodepleted red cells represented 100 per cent of total red cell volumes in 2009‐10, up from 86 per cent in 2008‐09 and 27 per cent in 2007‐08:

: This reflects the 2007 policy decision to move supply to 100 per cent leucodepleted;

not uncommon cardiac conditions such as atrial fibrillation, and patients with cerebrovascular diseases (for example, stroke). (NBA Monograph Series 2010 Prothrombinex‐VF, p5).

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platelets—whole blood leucodepleted pooled platelets make up 62 per cent and apheresis leucodepleted platelets make up 37 per cent of all platelet products in 2009‐10. In 2010‐11 these proportions are expected to be 55 per cent and 45 per cent respectively, indicating growth in the proportion of apheresis platelets;

FFP—the main volume is attributed to whole blood clinical FFP – buffy coat poor, at 85 per cent of total FFP in 2009‐10.

The current rates of use of the major fresh blood products on a per population basis can also be seen from Table 9 below.

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RECENT TRENDS IN FRESH BLOOD PRODUCT VOLUMES

TABLE 9: FRESH BLOOD PRODUCT VOLUMES AND GROWTH RATES, 2003‐04 TO 2009‐10

Product 2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Whole Blood Products 1,404 1,397 1,509 1,145 801 124 18

Average growth:

‐51.62 per cent

‐0.50 % 8.02 % ‐24.12 % ‐30.04 % ‐84.52 % ‐85.48 %

Red Cell Products 736,808 744,250 757,034 777,972 768,919 793,480 795,892

Average growth: 1.29

per cent

1.01 % 1.72% 2.77% ‐1.16% 3.19% 0.30%

Platelet Products 97,398 102,742 109,132 113,579 116,664 118,248 128,495


per cent

5.49% 6.22% 4.08% 2.72% 1..36% 8.67%

Fresh Frozen Plasma 138,287 138,842 142,450 141,397 144,987 152,689 160,813


per cent

0.40% 2.60% ‐0.74% 2.54% 5.31% 5.32%

Cryoprecipitate Products 33,343 38,342 43,251 49,679 53,459 59,267 64,734


per cent

14.99% 12.80% 14.86% 7.61% 10.86% 9.22%

Cryo‐depleted Plasma

Products

12,257 14,339 19,267 12,466 14,888 15,430 11,872


per cent

16.99% 34.37% ‐35.30% 19.43% 3.64% ‐23.06%

Other Fresh Products 10,491 8,007 8,190 8,705 6,371 6,629 8,377


per cent

‐23.68% 2.29% 6.29% ‐26.81% 4.05% 26.37%

Plasma for Fractionation 294,522 308,000 308,348 329,331 352,781 380,500 451,000


per cent

4.58% 0.11% 6.80% 7.12% 7.86% 18.53%


Rates of growth among the major fresh blood products have been relatively low overall, for example, red cell use has grown just over 1 per cent per annum (Table 9 above and Figure 20).

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FIGURE 20: VOLUMES OF SELECTED FRESH BLOOD PRODUCTS, 2003‐04 TO 2009‐10


Platelets growth per annum has averaged around 4.7 per cent. However, the year on year pattern has been variable. For example, the volume of platelet issues rose by only 1.36 per cent in 2008‐09, while it rose more than 8 per cent in 2009‐10.

There continues to be strong growth in major areas of platelet use, namely:

haematology/oncology, which accounts for around two thirds of platelet use; and

major surgery, particularly cardiac surgery, which is the next biggest user).

At the same time, the short shelf life of platelets, varying surgical practice and other inter‐jurisdictional differences in relation to platelet use, may explain an uneven pattern in demand growth.

There continues to be considerable jurisdictional variation in the type of platelet component supplied (that is pooled versus apheresis platelets). Variations in external expiry (in part due to geographic factors) and potential variations in clinical practice (such as use of anti‐platelet therapy, some variation in surgical, especially cardiac surgical, and transplantation practices) are known to exist. It is also possible that differing platelet products lead to variable rates of alloimmunisation and refractoriness to platelet transfusion, and therefore variable platelet consumption, in selected patient groups. Continuing strong focus on promoting appropriate transfusion practices and the implementation of leucodepletion of 100 per cent of red cells and platelets and an increase percentage of apheresis platelets has the potential to result in a reduction in the number of patients who become refractory to platelet transfusion due to alloimmunisation, thereby potentially reducing overall platelet demand.

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FFP total volumes have grown at an average annual rate of around 2.6 per cent (Table 9).

Reflecting the low rates of growth in volume, rates of use on a per population basis have remained reasonably stable over the period for each of red cells and platelets (Table 10). The rate of use for FFP per 1000 population has grown at a very small rate of just under 1 per cent per annum over the period.

TABLE 10: ISSUES OF FRESH BLOOD PRODUCTS PER 1000 POPULATION, 2003‐04 TO 2009‐10

Product 2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Whole Blood 0.07 0.07 0.07 0.06 0.04 0.01 0.00

Red Cell

Products

37.13 37.06 37.23 37.70 36.64 37.09 36.40

Platelet

Products

4.91 5.12 5.37 5.50 5.56 5.53 5.88

FFP 6.97 6.91 7.00 6.85 6.91 7.14 7.35

Cryoprecipitate 1.68 1.91 2.13 2.41 2.55 2.77 2.96

Cryo‐depleted

Plasma

0.62 0.71 0.95 0.60 0.71 0.72 0.54

Other Products 0.53 0.40 0.40 0.42 0.30 0.31 0.38

Plasma for

Fractionation

14.84 15.34 15.16 15.96 16.81 17.78 20.62

Source: NBA National Supply Plan and Budget, actual volumes, ABS catalogue 3101.0 – Australian Demographic Statistics.

Some stakeholders believed that a contributing factor to the growth in FFP use may be ‘Massive Transfusion’ protocols. In essence, these protocols call for a 1:1:1 rate of transfusion for red cells, platelets and FFP in the case of massive bleeding (such as in trauma cases). Other reasons may include use of FFP for warfarin reversal and high rates of wastage, as plasma is sometimes thawed and not used. The Blood Service data on wastage rates show FFP wastage higher than that for red cells in all jurisdictions except WA (Table 7 above), despite the product having a much longer shelf life. Wastage in NT in 09‐10 was close to 50 per cent of product issues. Progressive uptake of the ANZSBT document, Thawed Plasma Components: A Framework for the Preparation, Use and Storage, released in April 2009 may help reduce this level of wastage.

NBA notes that the use of FFP for plasma exchange in blood type mismatched renal transplants has placed increased pressure on FFP supplies. (National Blood Authority, Undated)

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PLASMA DERIVED PRODUCTS

As indicated above, plasma derived products are produced by CSL Ltd from the intermediate fresh blood product, plasma for fractionation. The main plasma derived products in the focus of this report are IVIg, albumin and Prothrombinex‐VF. Of the plasma derived group, these three products have wide application, on a population basis if not clinical indication basis. The other categories of plasma derived products have well‐defined uses for smaller, specific populations. The clotting factors are an example, which are used by people with haemophilia. Anti‐D immunoglobulin is a plasma‐derived product that is used to prevent sensitization of Rh(D) negative mothers, and prevent haemolytic disease of the newborn (HDN). The hyperimmune class of products are all specialist products used for the treatment or prevention of specific infective conditions, viral or bacterial, for example, tetanus.

IVIg is an immunoglobulin preparation for intravenous use. It can be used for replacing Immunoglobulin in both inherited and acquired immune deficiencies, modulate immunological/antibody mediated diseases (autoimmune diseases), either acutely (for example, thrombocytopenia) or chronically (for example, CIDP):

replace immunoglobulins in a number of inherited primary immune deficiency conditions;

treat acute and chronic autoimmune diseases; and

treat rare or debilitating mainly neurological and immunological conditions.

In Australia, IVIg is used to treat more than 90 conditions17, the vast majority of which fall within the three disciplines of haematology, immunology and neurology (Department of Health and Ageing, 2010). Neurological use is the single main indication.

Albumin 20 per cent is indicated, mainly, in the management of critically ill patients with extremely low albumin or burns. Albumin 4 per cent is indicated, mainly, in the management of shock associated with significant hypoalbuminaemia, for fluids maintenance, therapeutic plasmapheresis and for ‘pump priming’ in cardiothoracic surgery (Australian Red Cross Blood Service, 2009).

Prothrombinex‐VF is a clotting factor concentrate which contains clotting factors II, IX and X, and some other agents. Historically, there was a modest use of Prothrombinex‐VF concentrate for haemophilia patients with inhibitors. This use has now been largely replaced by the use of rFVIIa and Factor Eight Inhibitor Bypass Agent (FEIBA) therapy. The principal use for Prothrombinex‐VF in Australia now is for warfarin reversal.

IVIg ultimately drives demand for collection of plasma for fractionation. In Australia, domestic production of IVIg has not kept pace with demand. The shortfall is made up each year by imported finished product. In 2009‐10, imported IVIg composed approximately 24 per cent of total IVIg used in Australia.

Albumin and Prothrombinex‐VF each have a marginal cost of production and an associated demand. However, they are, in one sense, by‐products of the production of IVIg.

17 IVIg use for the majority (approximately two‐thirds) of these conditions is funded under the National Blood Budget. IVIg use for the remaining conditions is funded by other means, for example, through direct hospital budgets.

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National volumes and rates of use per 1000 population for the plasma derived products for 2009‐10 are indicated in Table 11.

TABLE 11: PLASMA DERIVED AND RECOMBINANT PRODUCT VOLUMES AND VOLUMES PER 1000 POPULATION, 2009‐10

Product or Product Group Units Volume Volume per 1000 population

Albumin g 6,741,994 308.29

Biostate IU 14,331,250 655.33

MonoFIX IU 2,655,000 121.41

Prothrombinex‐VF x500 IU 31,880 1.46

Thrombotrol x1000

IU

812 0.04

Domestic IVIg (Intragram) g 2,022,237 92.47

Imported IVIg g 630,762 28.84

Rh (D) IU 71,102,000 3253.75

WinRho SDF IU 141,000 6.45

CMV Immunoglobulin 30mL 1,764 0.08

Hepatitis IU 2,224,300 102.00

Normal Immunoglobulin mL 102,022 4.67

Tetanus IMIG x250IU 4,077 0.19

Tetanus IV x4000IU 59 0.00

Zoster 1g 2mL 1,287 0.06


RECENT TRENDS IN PLASMA DERIVED PRODUCT VOLUMES

In contrast to the main fresh blood products, absolute volumes of plasma derived products have been growing strongly over the period 2003‐04 to 2009‐10 (Table 12).

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TABLE 12: VOLUMES AND GROWTH RATES FOR SELECTED PLASMA DERIVED PRODUCTS, 2003‐04 TO 2009‐10

Product 2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Albumin* (kg) 4,097 4,181 4,836 5,311 5,829 6,297 6,742


per cent

2.03% 15.68% 9.82% 9.76% 8.02% 7.07%

Prothrombinex‐VF 6,831 10,188 12,858 16,782 21,202 26,541 31,880


per cent

49.14% 26.21% 30.52% 26.34% 25.18% 20.12%

Domestic IVIg (Intragam,

kg)

1,342 1,353 1,359 1,567 1,757 1,718 2,022


per cent

0.86% 0.44% 15.31% 12.14% ‐2.25% 17.72%

Imported IVIg (kg) 4.7 13.5 283.9 327.9 386.4 657.3 630.8


per cent

188.28% 1995% 15.50% 17.83% 70.12% ‐4.04%

Total IVIg (kg) 1,346 1,367 1,643 1,895 2,144 2,375 2,653

Average growth:

11.97 per cent

1.51% 20.22% 15.34% 13.12% 10.79% 11.70%

* Albumin group, that is including Albumin (4) and (20).


Intravenous Immunoglobulin (IVIg)

The national issue of IVIg has grown from 1.3 million to 2.7 million grams in 2009‐10, representing an average annual growth rate of 12 per cent. IVIg use has been growing on a per population basis as well. It was 67.84g in 2003‐04 and grew to 121.33g in 2009‐10. This represents an increase of around 10 per cent per year on average.

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TABLE 13: VOLUMES PER 1000 POPULATION, SELECT PLASMA DERIVED PRODUCTS 2003‐04 TO 2009‐10

Product 2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Albumin (g/1000) 206.48 208.18 237.80 257.37 277.77 294.31 308.33

Prothrombinex‐VF

(x500IU/1000)

0.34 0.51 0.63 0.81 1.01 1.24 1.46

Domestic IVIg (g/1000) 67.61 67.38 66.83 75.95 83.74 80.29 92.48

Imported IVIg (g/1000) 0.24 0.67 13.96 15.89 18.41 30.72 28.85

Total IVIg (g/1000) 67.85 68.05 80.79 91.84 102.15 111.01 121.33

Rh(D) (Total) (IU/1000) 2075.06 2557.34 2994.84 3322.49 3277.30 3278.22 3258.11

Source: NBA National Supply Plan and Budget, actual volumes, ABS catalogue 3101 – Australian Demographic Statistics.

Demand for IVIg has corresponded to increased use for indicated medical conditions, principally in the areas of haematology and neuropathy. This will be discussed in more detail below.

Albumin

The volume of total albumin (4 per cent and 20 per cent products) has grown on average annually at a rate of over 8 per cent over the period 2003‐04 to 2000‐10.

On a per population basis, albumin use has also been growing strongly (Table 13), at an average of 7 per cent annually. There has been steady growth in the use of albumin in Australia since the Saline versus Albumin Fluid Evaluation (SAFE) study, May 2004 (Safe, 2004). The SAFE study indicated that use of either 4 per cent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. Growth in albumin use had declined from 1998 till then, following the publication of Cochrane Injuries Group Albumin Reviewers, Human albumin administration in critically ill patients: systematic review of randomised controlled trials, July 1998 (Cochrane Injuries Group, 1998). This study had found that for each patient category the risk of death in the albumin treated group was higher than in the comparison group.

However, the steady growth continued from 2004‐05 despite the SAFE Investigators issuing a subsequent report in 2007 (Myburgh, 2007), which noted that the 2004 SAFE study suggested that patients with TBI resuscitated with albumin had a higher mortality rate than those resuscitated with saline. The SAFE Investigators conducted a post hoc follow‐up study of patients with TBI who were enrolled in the SAFE study. Then, in June 2009, Access Economics (Access Economics, 2009) conducted a study on the economic cost of spinal cord injury and TBI in Australia for the Victorian Government Neurotrauma Initiative. This looked at the use of albumin in the treatment of TBI. The authors found that, in Victoria alone, noting that the lower mortality rate with the use of saline as compared to albumin would save costs such as productivity losses and burden of diseases due to premature death,

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presented the fact (from their Cost effectiveness Analysis [CEA]) that, based on economic modelling, the total estimated Disability Adjusted Life‐Years (DALYs) averted were 17,915 with a net benefit of $687.7 million.

Looking at the steady growth rate in albumin use in all jurisdictions, it is possible that clinical use of albumin in Australia is still being driven by the SAFE study findings rather than more recent findings, especially those in relation to the use of Albumin 4 per cent in TBI.

There was no information available to the project to enable analysis of what has been driving the growth in albumin use. For example, no data was found detailing the clinical uses of albumin, or the characteristics of the patient groups being treated with the product. Given the evidence cited above which indicates that saline could be a cheaper, equally efficacious alternative to albumin, it would be valuable to have data which could show whether albumin is being used for indications for which saline could be substituted.

For most hospitals in Australia, even though saline is relatively cheap, albumin is effectively a free good. This is because albumin (along with other blood products) is paid for by Australian governments centrally through NBA, and supplied to the hospital free of charge. There are several observations from the data which could indicate that the choice of albumin use over saline is influenced by the lack of a price signal on albumin18. Two examples, which will both be discussed further below, are:

hospital separations associated with transfusion of ‘other serum’ (which includes albumin) have grown faster in the private sector than in the public (Table 19, p86);

albumin use per population in NSW has been substantially lower than that in the other large states (Table 17, p.62). In NSW, public hospitals do confront a price signal for albumin (and other blood products) due to the devolved state blood budget.

Prothrombinex VF

Volumes of Prothrombinex‐VF grew markedly from over the period 2003‐04 to 2009‐10, at an average annual growth rate of around 29 per cent. It grew 49 per cent in the single year to 2004‐05. Since 2006‐07, the annual rate of growth rate has started to taper. Between 2008‐09 and 2009‐10, the rate of growth in issues was nevertheless still strong at 20 per cent.

On a per population basis, the rate of growth is also very strong. Prothrombinex‐VF issues per 1000 population have climbed from 0.34 to 1.46 over the period, representing a 27 per cent increase on average annually.

The principal use of Prothrombinex‐VF in Australia is for warfarin reversal. Although FFP contains all the clotting factors that are reduced by warfarin therapy, Prothrombinex‐VF is usually preferred, at least as a source of factors II, IX and X, for two reasons (National Blood Authority, 2010), namely:

given the clotting factors in Prothrombinex‐VF are more concentrated, the total intravenous fluid volume of Prothrombinex‐VF that needs to be administered is much less than the equivalent amount of FFP that would need to be transfused to achieve the same degree of reversal. This has advantages in some situations, especially in patients

18 Price signals in the blood sector are discussed in more detail in the Sapere report on Options to Manage Appropriate Use of Blood and Blood Products.

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with acute renal failure or those with raised intracranial pressure, who may tolerate a volume load poorly;

there is a small risk of transfusion related acute lung injury (TRALI) associated with the transfusion of FFP (to all recipients, not just to those receiving it as a part of warfarin reversal). There is preliminary data to suggest that for some patients clinically adequate warfarin reversal may be achieved with the use of Prothrombinex‐VF alone, without the addition of FFP as an additional source of Factor VII.

From January 2005, following the promulgation of the Consensus Guidelines on warfarin Reversal (Baker, 2004), demand for Prothrombinex‐VF increased almost four‐fold. However, the rate of uptake of the guidelines between jurisdictions has varied considerably. The highest uptake has been in Victoria and the lowest in the NT and NSW. Some stakeholders speculated that the slower rate of uptake in NSW may be related to the fact that NSW has devolved their blood budgets to AHS. As a result, hospitals may be choosing the cheaper FFP product over Prothrombinex‐VF. As will be seen below, issues to Victoria are more than double that of any other jurisdiction.

There is a lack of data on the use of Prothrombin complex overseas.

RECOMBINANT PRODUCTS

Recombinant products are genetically engineered products used mainly in the treatment of haemophilia. Recombinant products are not derived from plasma. However, the class of products has historically been included among blood products in Australia. This is because they are usually stored in a blood bank and managed by haematologists. Australia imports all of its recombinant products.

The main recombinant products are the clotting factor concentrates Recombinant Factors VIIa, VIII and IX.

RFVIIa usage is difficult to analyse as it is dependent on the number of haemophilia‐with‐inhibitor patients in each State, their age and weight. Most use of recombinant factors is on demand, that is, there is no consistent clinical usage pattern. While some of the clotting factors are administered prophylatically, this element is small. The population group is small and defined. The total number of persons registered with Haemophilia A is approximately 2400. A smaller proportion of this number has a severe condition that requires regular treatment. The numbers of Haemophilia B persons registered is approximately 570. Again, a smaller proportion of these have a severe condition, which requires frequent treatment. The numbers registered with Von Willebrand Disease is approximately 2000, although the clinical condition is mild and may require therapy very infrequently, particularly of blood products.

As a consequence of these small numbers, bleeding and treatment episodes of individual patients can distort the usage patterns year on year.

The variability in usage is evident in Table 14 below.

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TABLE 14: VOLUMES OF ISSUE OF RECOMBINANT PRODUCTS, 2009‐10

Recombinant Product Unit Volume Volume per 1000 population

BeneFix (rFIX) IU 22,566,500 1032.02

Novoseven (rFVIIa) IU 23,895 1.09

Recombinant Factor VIII (rFVIII) IU 127,321,750 5822.73

Source: NBA National Supply Plan and Budget 2003-04 to 2009-10,ABS catalogue 3101.0 – Australian Demographic Statistics.

The variability in use is also evident in the volumes on a per population basis (Table 15).

TABLE 15: RECOMBINANT PRODUCT VOLUMES OF ISSUE PER 1000 POPULATION, 2003‐04 TO 2009‐10

Product 2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

BeneFix (rFIX) 246 478 687 704 883 1036 1032

Novoseven (rFVIIa)

0.78 0.94 1.14 1.27 0.79 0.76 1.09

rFVIII 1753 3318 4334 4871 5486 5676 5822

Source: NBA National Supply Plan and Budget, actual volumes, ABS catalogue 3101.0 – Australian Demographic Statistics.

Plasma derived substitutes are produced domestically for the clotting factors Factor VIII and Factor IX. The recombinant Factors VIII and IX are used overwhelmingly in favour of the plasma derived Factors, with recombinant imports being used in nearly eight times the volume of domestically produced plasma‐derived factors (as measured by total IUs) in 2009‐10 for both Factors VIII and IX. This pattern of usage follows a policy decision in 2005 for recombinant products to be available to all as the existing plasma derived product Biostate was experiencing limited supply and continuing possible risk of carrying the virus CJD.

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FIGURE 21: VOLUMES FVIII, RECOMBINANT AND PLASMA DERIVED, 2003‐04 TO 2009‐10


Wastage of recombinant products can be an issue, particularly in regard to guaranteeing access to emergency supplies in regional and remote areas. No data was available to quantify the extent of recombinant product wastage.

STATE AND TERRITORY PATTERNS OF BLOOD USE

The most distinct observations in the data are the marked differences in usage patterns among the states and territories for individual products. Table 16 provides a breakdown of the current use of blood products for each of the states and territories.

0

20

40

60

80

100

120

140

160

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Millions of IU

Recomb Factor VIII

Biostate 500 IU

Biostate 250 IU

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TABLE 16: VOLUMES (STANDARD UNITS) OF SELECT FRESH AND PLASMA‐DERIVED PRODUCTS BY STATE AND TERRITORY, 2009‐10

Product ACT NSW NT QLD SA TAS VIC WA Total

Red Cell Products 12,535 247,432 5,278 169,139 71,226 15,235 207,004 68,044 795,892

Platelet Products 2,066 35,192 868 35,958 9,661 2,792 33,043 8,915 128,495

FFP 2,234 57,923 574 38,405 14,566 1,503 32,887 12,722 160,813

Cryoprecipitate 1,409 25,333 285 9,139 2,716 1,472 18,450 5,885 64,734

IVIg (kg) 44.8 920 8.61 639 174.5 78.8 607.8 179.2 2,653

Albumin (kg) 136.5 1873 46.9 1734 531.5 142 1820 458.4 6,742

Prothrombinex‐VF 1149 6050 188 5453 2490 928 12711 2911 31,880

Rh(D) (x1000 IU) 1432 21,870 688 15,425 5586 1820 16,681 7600 71,102.


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In the main, absolute volumes are driven by the relative population sizes of the States. So NSW generally dominates absolute volumes (Figure 22).

Lower volume products, such as the clotting factors, can be influenced by the pattern of residence of user populations, particularly haemophiliacs, and the medical history of individual recipients.

FIGURE 22: SELECTED BLOOD PRODUCTS, STATE AND TERRITORY RELATIVE VOLUMES, 2009‐10


To enable comparisons of use by jurisdiction, this report looks at relative growth rates in absolute volumes and also volumes consumed on a per population basis below.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

WA

VIC

TAS

SA

QLD

NT

NSW

ACT

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TABLE 17: VOLUMES PER 1000 POPULATION BY STATE AND TERRITORY, SELECTED PRODUCTS, 2009‐10

Product

Group

ACT NSW NT QLD SA TAS VIC WA National

Red Cell

Products

35.69 34.80 23.53 38.42 43.97 30.32 38.17 30.45 36.40

Platelet

Products

5.88 4.95 3.87 8.17 5.96 5.56 6.09 3.99 5.88

FFP 6.36 8.15 2.56 8.72 8.99 2.99 6.06 5.69 7.35

Cryoprecipi

tate

4.01 3.56 1.25 2.06 0.95 2.93 3.21 2.60 2.85

IVIg (g) 127.48 129.40 38.38 145.25 107.73 156.83 112.08 80.20 121.33

Albumin 388.55 263.43 209.22 393.99 328.13 282.63 335.54 205.13 308.33

Prothrombi

nex‐VF

3.27 0.85 0.84 1.24 1.54 1.85 2.34 1.30 1.46

Rh(D) 4077 3084 3069 3516 3449 3635 3081 3402 3258



The different jurisdictions use fresh blood products in differing intensities (Figure 23 and Figure 24), although SA records the highest rates of use per 1000 population for both red cells and FFP.

FIGURE 23: RED CELL USE PER 1000 POPULATION BY STATE AND TERRITORY, 2009‐10


0

5

10

15

20

25

30

35

40

45

50

Red Cells

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

Overall

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FIGURE 24: ISSUES PER 1000 POPULATION BY STATE AND TERRITORY, SELECTED FRESH BLOOD PRODUCTS, 2009‐10


Red cells

The growth rates in the volume of red cell issues for the states and territories have been reasonably flat and reasonably consistent over the period. This would suggest that growth in red cell issue at the national level reflects the sum of all jurisdictions, rather than being driven disproportionately by any one or several jurisdictions.

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

Platelets FFP Cryoprecipitate

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

National

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FIGURE 25: RED CELL ISSUES PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


The most prominent point of difference amongst the jurisdictions is, however, the degree to which red cell use per population in SA stands above the other jurisdictions. In 2009‐10, the rate of use per 1000 population was 43.97 units, compared with the next highest per 1000 population rates of 38.42 recorded for Queensland. In contrast, NSW, the largest state, recorded use of 34.8 units per 1000 population. Of the states, WA and Tasmania recorded the lowest rates at around 30.45 and 30.32 units respectively.

Among the larger states, as mentioned, Queensland and Victoria have a similar level of use of red cells on a per population basis. This has remained close over the period 2003‐04 to the present. NSW’s per population usage has tracked below that of Victoria and Queensland over this period.

There was insufficient data to be able to explain the differences in usage patterns among the jurisdictions. Factors would include the relative age profiles and incidence of medical conditions strongly associated with transfusion. For instance, SA has an older age profile than all States except Tasmania. However, age profiles alone do not account for the differences: Tasmania’s use of red cells per population is much lower than that in SA.

A study by SA Health in 2009 (based on 2006 data) into that state’s relatively high use of red cells noted that the results of benchmarking against NSW showed that if South Australian public hospitals had had the same activity adjusted utilisation rate as the NSW state average in 2006, they would have used approximately 3 per cent more red cells than they actually did. That is, SA’s public sector utilisation rate (based on the selected subset for consistent comparison) is lower on a casemix adjusted activity basis than the NSW state average subset (South Australian Department of Health, 2009).

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Differences in per population use of red cells might be explained also by different clinical practice and different emphases in appropriate use programs. However, the detailed information to confirm this was not available.

The question of the effectiveness of appropriate use programs is taken up in more detail in the Options to Manage Appropriate Use of Blood and Blood Products report. In general, there was very little information on this topic. However, some prima facie observations can be made from the data that do exist. There was a significant drop in red cell use on a per population basis in NSW in 2007‐08 and it has remained below the 2006‐07 for the rest of the period. This coincided with the implementation of a number of initiatives, including:

broad implementation of hospital pre‐admission clinics with the identification and management of anaemia, including iron‐deficiency anaemia;

establishment of the NSW CEC’s Blood Watch Program promoting appropriate use;

devolution of the NSW blood budget to area health services.

In Tasmania, red cell use declined over the period in question. Contributing factors towards the end of this period may include the presence of transfusion nurses in major public hospitals, and a targeted program to reduce discard of red cells. This involved memoranda of understanding (MOU) between hospitals, which are facilitated by the Blood Service. However, the information was not available to explain the declining trend over the full length of the period in question.

Platelets

Again, the most distinct observation is the degree to which a single State, in this case Queensland, stands above the others in terms of its use of a product on a per population basis. Figure 26 shows that this relativity has maintained over recent history.

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FIGURE 26: ISSUES OF PLATELETS PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


Notable, too, is the degree of difference between the rate of per population use in NSW compared with the states of Victoria and Queensland. NSW’s rate of use was 4.95 in 2009‐10, compared with 8.17 in Queensland and 6.09 in Victoria.

Overall, the rates of growth in use of platelets on a per population basis vary amongst the jurisdictions. For example, Victoria has experienced a steady growth in platelet issues; WA has kept its use relatively stable and NSW has risen and fallen.

There continues to be considerable jurisdictional variation in the type of platelet component supplied (that is, pooled versus apheresis platelets). Variations in external expiry (in part due to geographic factors) and potential variations in clinical practice (such as use of anti‐platelet therapy, some variation in surgical, especially cardiac surgical, and transplantation practices) are known to exist.

It is also possible that differing platelet products lead to variable rates of alloimmunisation and refractoriness to platelet transfusion, and therefore variable platelet consumption, in selected patient groups. Continuing strong focus on promoting appropriate transfusion practices and the implementation of leucodepletion of 100 per cent of red cells and platelets and an increased percentage of apheresis platelets has the potential to result in a reduction in the number of patients who become refractory to platelet transfusion due to alloimmunisation, thereby potentially reducing overall platelet demand.

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Fresh frozen plasma

A notable observation is the relatively steep rise in use of FFP, per 1000 population, in SA from 2006‐07 onwards (Figure 27). SA currently has the highest rate of FFP use on a per population basis, whereas it ranked fourth at the beginning of the period.

Queensland appears to have begun to match this rate of growth from 2007‐08. As a result, SA and Queensland have both overtaken NSW as the traditionally highest user of FFP on a per population basis (excepting the highly variable trend in NT). The rates of use were very similar in 2009‐10 between these three jurisdictions.

FIGURE 27: ISSUES OF FRESH FROZEN PLASMA PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


There is a distinct divergence, however, in the rates of per population usage of FFP for these three states (SA, Queensland and NSW), from WA and Victoria.

Differing clinical practice may influence use of FFP. For example, for patients on warfarin therapy, in circumstances where there is active bleeding, or there is a need for an urgent invasive procedure, or the INR test (the laboratory test that is performed to monitor the warfarin therapy) shows a very high result, the current guidelines recommend the use of FFP and Prothrombinex‐VF, in addition to vitamin K to reverse the warfarin effect. However, uptake of this recommendation has not been consistent across the country. Some stakeholders believed that institutions in NSW prefer to use FFP rather than Prothrombinex‐VF for warfarin reversal, as FFP is a cheaper product. This choice may be influenced by the NSW blood budget being devolved. NSW has maintained a relatively high rate of FFP use per

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population and, as will be seen below, the lowest rate of use of Prothrombinex‐VF over the period.

In other jurisdictions there are some physicians of the opinion that FFP may not be required in addition to Prothrombinex‐VF in all such cases (National Blood Authority, Undated – a).

Increasing adoption of massive transfusion protocols with earlier, more aggressive management with platelets and plasma is likely to increase FFP demand as well as creating the necessity to review the sites where FFP inventories are held.



IVIg use has grown strongly in all jurisdictions. Over the period 2003‐04 to 2009‐10, the average rates of growth were strongest in NSW (19 per cent) and Queensland (18 per cent). Growth in Victoria was approximately 14 per cent. However, even in NT and WA which experienced the slowest rates of growth (9 and 10 per cent per annum respectively), the rates of growth were still high.

FIGURE 28: IVIG ISSUES PER STATE AND TERRITORY, 2003‐04 TO 2009‐10


The current AHMC approved Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) (‘the IVIg Criteria’) were issued in December 2007. Prior to the release of the IVIg Criteria, growth in IVIg usage approximated 12 per cent per annum between 2003‐4 and 2007‐08. Since then, growth has averaged 11 per cent per annum.

The IVIg Criteria are currently under review, including a literature review and an IVIg cost‐effectiveness review. The IVIg Criteria expanded the range of indications for IVIg, but also tightened the process of approval for use. The IVIg Criteria are to be used by clinicians for the use of government subsidised IVIg, and are based on the strength of the evidence

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

1,000,000

Volume (g)

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

P a g e | 69

supporting the use of IVIg for certain clinical conditions. Within the IVIg Criteria , Section 5 conditions generally have a strong evidence base, and represent 83 per cent of product use; Section 6 conditions have a lesser evidence base, and represent 14 per cent of usage; Section 7 conditions have a poorer evidence base and IVIg is issued under Section 7 only in individual exceptional circumstances to treat mostly rare and debilitating conditions (these conditions represent approximately 2 per cent of product use). Subsidised IVIg is not available for Section 8 conditions.

The Blood Service Transfusion Medicine Team (TMT), in a ‘gatekeeper’ role, provides a consultancy service and issues IVIg based on clinical need. As indicated earlier, the Blood Service must approve all requests for use of IVIg.

The Blood Service reported in 2010 (Australian Red Cross Blood Service, 2010c) that the growth in IVIg use in Queensland was attributed to growth in the number of patients receiving the treatment with acquired immune deficiency secondary to haematological malignancies (AHSHM) as well as the number of patients with CIDP having grown significantly in Queensland in recent years relative to other states. In Queensland, the major proportion of patients over 50 years on IVIg treatment fall in the haematology category.

Conversely, the Blood Service reports, that IVIg use has declined in WA in recent years and indicates that it has had a lower growth of new patients with the top two disease groups AHSHM and CIDP. However, WA has also piloted an Ideal Body Weight program, which responds to the problem of increasing rates of obesity in the population.

On a per population basis, Tasmania has consistently been the highest user jurisdiction of IVIg over the period 2003‐04 to 2009‐10. Use per 1000 population in 2009‐10 was estimated at 157 grams, compared with a national average of 121 grams (Table 17). Tasmania is a small jurisdiction and the IVIg issue rates expressed as a proportion of a small base make it difficult to compare the trend with other, larger jurisdictions.

FIGURE 29: USE OF IVIG PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


0

20

40

60

80

100

120

140

160

180

Volumer per 1000 population (gram

s)

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

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On the other hand, the larger state of Queensland recorded the next highest use of IVIg on per population basis in 2009‐10, at 145.25g per 1000. This is also significantly above the national average. Queensland’s use of IVIg on a per population basis has consistently been above the national average over the period. It has also consistently been high in relation to the other large States.

The Blood Service highlights that differences in the patient mix can affect the volume of IVIg per jurisdiction. For example, those jurisdictions with a higher proportion of CIDP patients on IVIg may have higher usage rates, as the dose frequencies are much higher than for the treatment of AHSHM. Usage rates per patient in Queensland and NSW fell below the national average over the period 2008‐2010. ACT, Tasmania, SA, WA and Victoria use per patient reached above the national average in the same period.

Albumin

The total volumes of albumin issue in each of the major jurisdictions have been growing steadily over the period. The growth in WA has not been as pronounced as in the large states.

FIGURE 30: ALBUMIN ISSUES BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


For the major jurisdictions again, there is consistency to the extent that the patterns of growth in terms of use on a per population basis show a general upward trend over the period (Figure 31).

0

1000

2000

3000

4000

5000

6000

7000

8000

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Volume of albumin (kg) WA

VIC

TAS

SA

QLD

NT

NSW

ACT

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FIGURE 31: ALBUMIN ISSUES PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


However, there are significant variations in the actual rates of use per 1000 population (Table 17 above).

Queensland records the highest use per 1000 population, at 393.99g in 2009‐10. This rate is significantly higher than the national average of 308.33g. It is also substantially higher than WA, which records use per 1000 population of 205.13g in 2009‐10, putting it at the bottom of all jurisdictions in that year.

A significant observation is that the rate of usage per 1000 population in NSW, the largest State, has tracked a path as the second lowest over the period.

No information on the breakdown of uses of albumin was available to the project.

Prothrombinex VF

From January 2005, following the promulgation of the Consensus Guidelines on Warfarin Reversal (Baker, 2004), demand for Prothrombinex‐VF increased almost four‐fold. However, the rate of uptake of the guidelines between jurisdictions has varied considerably. As was noted earlier, growth in Prothrombinex‐VF use at a national level has been very high in recent history. This strong growth is echoed in all jurisdictions (Figure 32). The most notable trend, however, is the take‐off in use in Victoria. The growth in use in Victoria has been more rapid and began earlier than any other jurisdiction.

0

50

100

150

200

250

300

350

400

450

500

Volume per 1000 population (gram

s)

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

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FIGURE 32: PROTHROMBINEX‐VF VOLUMES BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


Use of Prothrombinex‐VF in Victoria outstrips all other jurisdictions by a significant amount. Victorian use accounted for about 40 per cent of national use in 2009‐10, which is disproportionately greater than its share by population.

On a per population basis, the ACT’s rate of use stands substantially above the other jurisdictions (Figure 33). The ACT is a very small jurisdiction and this can distort the apparent pattern of use.

There was a wide variation between the jurisdictions in 2009‐10 in use per 1000 population. Rates of use range from 0.84 and 0.85 units per 1000 in NSW and NT respectively, up to 2.34 and 3.27 units per 1000 population in Victoria and ACT respectively (Table 17).

As was indicated earlier, the low rate in NSW may be influenced by the use of FFP as a preferential product for warfarin reversal.

0

5000

10000

15000

20000

25000

30000

35000

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Volume (X500IU)

WA

VIC

TAS

SA

QLD

NT

NSW

ACT

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FIGURE 33: PROTHROMBINEX‐VF VOLUME PER 1000 POPULATION BY STATE AND TERRITORY, 2003‐04 TO 2009‐10



The most notable features of use patterns of the recombinant products are:

the high rate of growth in the use of rFVIII—the use of the recombinant factor has substituted for plasma derived FVIII (Figure 34);

the degree of variability in the use of rFVIIa (Figure 35).

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FIGURE 34: VOLUME OF ISSUES RECOMBINANT FACTOR VIII, BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


FIGURE 35: RECOMBINANT FVIIA VOLUME, BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


The usage rates of rFVIIa on a per population basis for these products are also highly variable, as they reflect a small population of recipients and their highly individualised needs.

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

10,000

Volume per 1000 population (IU)

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

0

5000

10000

15000

20000

25000

30000

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

Volume (mg)

WA

VIC

TAS

SA

QLD

NT

NSW

ACT

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FIGURE 36: RECOMBINANT FVIIA, VOLUME PER 1000 POPULATION, BY STATE AND TERRITORY, 2003‐04 TO 2009‐10

Source: NBA National Supply Plan and Budget, 2003-04 to 2009-10; ABS Catalogue 3101.0 – Australian Demographic Statistics.

USAGE PATTERNS INDICATED BY HOSPITAL SEPARATIONS

DATA CONSIDERATIONS

Hospital separations are coded for the infusion19 of certain categories of blood products, including red cells (coded as ‘packed cells’), platelets, IVIg (coded as ‘gamma globulin’), coagulation factors (which cover the clotting factors, including Prothrombinex‐VF), and ‘other serum’ (which includes albumin and FFP).

The dataset examined for this report pertained to 2003‐04 to 2008‐09 (the latest separations data available).

As the codes pertain to groups of products, it was not always possible to distinguish independently the trends for separations involving individual products of interest in this report, namely albumin, FFP, Prothrombinex‐VF or any other of the individual clotting factors.

The hospital separations dataset was an important source for gaining some insight into relative patterns of use between the private and public sectors. Analysis in this area is taken up further below.

19 ‘Infusion’ is used interchangeably with ‘transfusion’ in this report.

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GENERAL TRENDS

Only a small proportion of hospital separations overall is associated with the transfusion of blood or blood products, 3.6 per cent in 2008‐09. Nevertheless, separations involving transfusion have climbed as a proportion of all separations over the period 2003‐04 to 2008‐09. In the five years between 2003‐04 and 2008‐09, total hospital separations rose by 19.1 per cent, whereas transfusion related separations grew by 26.5 per cent. The pattern of proportional growth is shown in Figure 37.

FIGURE 37: SEPARATIONS INVOLVING TRANSFUSION AS A PROPORTION OF ALL SEPARATIONS, 2003‐04 TO 2008‐09

Source: National Admitted Patient Care Collection, 2003-04 to 2008-09, Department of Health and Ageing

In 2008‐09, transfusion of red cells accounted for the majority (58 per cent) of separations involving transfusion (Figure 38). The next highest transfusion types were IVIg at 15 per cent and ‘Other Serum’ (including albumin and FFP) at 12 per cent. This distribution gives a dimension of hospital activity levels attributable to the transfusion of the various blood products, which is not apparent from examining figures on volume of product issue.

3.25%

3.30%

3.35%

3.40%

3.45%

3.50%

3.55%

3.60%

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09


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FIGURE 38: NATIONAL SEPARATIONS BY TRANSFUSION TYPE, 2008‐09


Separations associated with transfusion have grown at differing rates depending on the product group. This is shown in Figure 39.

Exchange Transfusion

0%

Tx of Autologous Blood3%

Tx of Blood Expander

2%

Tx of Coagulation Factors1%

Tx of Gamma Globulin15% Tx of Leukocytes

0%

Tx of Other Serum12%

Tx of Other Substance

0%

Tx of Packed Cells58%

Tx of Platelets

8%

Tx of Whole Blood1%

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FIGURE 39: NATIONAL SEPARATIONS BY TRANSFUSION TYPE, PERCENTAGE CHANGE 2003‐04 TO 2008‐09


The patterns of growth evident in the number of transfused separations broadly support the patterns of growth in volume that were identified for each of the main product groups earlier in this report. For example, separations associated with transfusion of red cells, platelets, ‘other serum’ (including FFP and albumin), IVIg and coagulation factors (including Prothrombinex‐VF) have all grown over the five‐year period in question.

A number of additional observations are made:

separations involving red cell transfusion grew at a faster rate (averaging around 2.7 per cent per annum) than total volume (on average 1.5 per cent) over the same period;

it is not possible to determine the breakdown of separations associated separately with FFP or albumin from the figures above. However, as the rate of growth in volume of albumin issues has exceeded that of FFP issues over the period, it suggests that the bulk of the growth in transfusions of ‘other serum’ would pertain to albumin use;

while the growth of separations involving blood expander has been very high, the absolute numbers of transfusions are very small. This is evident in Figure 38 above;

this is true also for separations involving coagulation factors, which made up only 1 per cent of all transfused separations in 2008‐09.

(100.0%) (50.0%) 0.0% 50.0% 100.0% 150.0%


Tx of Autologous Blood


Tx of Coagulation Factors


Tx of Leukocytes

Tx of Other Serum


Tx of Packed Cells

Tx of Platelets

Tx of Whole Blood

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STATE AND TERRITORY TRENDS

As with patterns of use according to the volume figures discussed earlier, there are wide variations among the jurisdictions in the patterns of transfusion related separations.

Figure 40 indicates that SA, Victoria and Queensland are the states with the highest ratios of separations involving transfusion of blood or a blood product. That is, these states exhibit the highest propensity for admitted patients to be transfused.

FIGURE 40: PROPORTION OF SEPARATIONS INVOLVING TRANSFUSION, BY JURISDICTION, 2008‐09


The national trend for transfused separations to grow as a proportion of all separations has not held in all states and territories (Figure 41). Significantly, NSW has gone against the trend, as have the small jurisdictions of ACT, NT and Tasmania. In Tasmania, the number of transfused separations has actually contracted over the period, while total separations have continued to grow.

0.0%

0.5%

1.0%

1.5%

2.0%

2.5%

3.0%

3.5%

4.0%

4.5%



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FIGURE 41: PERCENTAGE CHANGES IN TRANSFUSED AND TOTAL SEPARATIONS BY JURISDICTION, 2003‐04 TO 2008‐09


There were also significant differences between jurisdictions on per population basis. This can be seen from the results in Table 18 and Figure 42 below.

TABLE 18: TRANSFUSED SEPARATIONS PER 1000 POPULATION, BY PRODUCT TYPE AND JURISDICTION, 2008‐09

ACT NSW NT Qld SA Tas Vic WA National


0.23

0.17

0.07

0.09

0.22

0.27

0.32

0.09

0.19


2.02

1.21

0.53

1.31

1.88

1.15

2.10

1.66

1.55

Tx of Other Serum

1.32

1.43

1.34

0.89

1.31

1.15

1.73

1.43

1.38

Tx of Packed Cells

6.19

6.27

4.78

5.14

8.27

4.81

6.99

5.68

6.26

Tx of Platelets 0.74

0.88

0.36

0.84

1.23

0.72

1.11

1.03

0.96

*Tx is an abbreviation for ‘transfusion’


Figure 42 compares separation rates per 1000 population by jurisdiction, for transfusion types accounting for 93 per cent of all transfusion‐related separations. The figure shows the relativity to the national average (index 1.0). Different states show different rates of separations involving transfusion according to the blood product in question.

Queensland stands out in terms of the number of separations per 1000 population involving transfusion of IVIg and platelets. This accords with relatively high rates of use per population, on the basis of volume of issues, for both products.

‐5%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%


Chan

ges

Total Separations Separations Involving Transfusion

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SA stands out in terms of the rate of transfusion of red cells and platelets, which again accords with per population volume of issue data.

Victoria is notable in terms of the rate of separations involving transfusion of Other Serum20 and also IVIg. Victoria has one of the highest rates per population of albumin use (volume of issues basis). However, interestingly, its rate is exceeded by those in ACT and Queensland.

FIGURE 42: TRANSFUSED SEPARATIONS PER 1000 POPULATION AS RATIO OF NATIONAL AVERAGE, SELECTED BLOOD PRODUCTS BY JURISDICTION, 2008‐09


Also of interest is the extent to which the rates of transfused separations per population in NSW fall below the national averages and below the rates of the other large jurisdictions, for each of the blood products appearing above, except Other Serum. The rate of separations involving transfusion of Other Serum per population is slightly higher in NSW than in Queensland. In NSW, this is likely to be affected by a relatively high rate of use (on volume of issues) per population for FFP.

The pattern of separations involving transfusion of IVIg per population in Tasmania is also interesting. Tasmania’s rate of use of IVIg per population has tracked significantly above all jurisdictions over the period 2003‐04 to 2009‐10, including in 2008‐09 (that is, the period of the data in Figure 42). However, IVIg‐transfused separations per population fell substantially below the national average in 2008‐09.

Similarly, while use of IVIg per population in WA, in terms of volumes of issue, was the lowest in 2008‐09 (excluding NT), WA had the third highest rate of IVIg transfused separations in that year.

As indicated in the earlier discussion of jurisdictional differences in IVIg use, some of these differences can be attributed to the mix of patients and IVIg dosage regimes. However, the degree to which these factors contribute to the differences is not clear.

20 Most likely to be attributable to albumin, as Victoria has a relatively low rate of FFP use per 1000 population based on volume of issue figures.

‐

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60



Tx of Other Serum

Tx of Packed Cells

Tx of Platelets

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PUBLIC‐PRIVATE SECTOR TRENDS

Data detailing aspects of use of blood and blood products by private sector health providers in Australia were not readily attainable. NBA national and jurisdictional data regarding volumes of blood products was not able to identify the respective volumes issued to private and public health providers. NBA advised that it did not hold any reliable or robust data, which could identify private sector blood issues.

The Blood Service was similarly unable to identify issues of blood and blood products to private hospitals.

Access was not available to sample data underpinning a prospective red cell audit conducted in Victoria in 2009 (known as the ‘Bloodhound study’ (Shortt, 2009)), which may have provided the public‐private breakdown of sample data collected on the clinical use of red cells in Victoria in 2007‐08.

Some indication of the relative use of blood and blood products between the public and private sectors is available from the hospital separations dataset. As was indicated earlier, these data show only the number of separations and contain no information on volumes of blood products transfused.

General trends

While the private sector accounted for 40 per cent of all hospital separations in 2008‐09, it accounted for only 32 per cent of transfused separations (Figure 43).

FIGURE 43: DISTRIBUTION OF TOTAL AND TRANSFUSED SEPARATIONS, PUBLIC AND PRIVATE SECTORS, 2008‐09


The public‐private split of separations involving transfusion remained relatively static over the period 2003‐04 to 2008‐09, both on a national and jurisdictional basis. The only significant change was in Tasmania, where the private sector proportion of transfusion‐related separations declined from 38 per cent in 2003‐04 to 29 per cent in 2008‐09.

Jurisdictional trends

There are significant differences in the patterns of private sector activity amongst the jurisdictions in transfused separations. Transfused separations were high per population in SA, Victoria and Queensland (Figure 44) in 2008‐09. However, the rate per population

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accounted for by the private sector in Queensland is substantially higher than in the other jurisdictions.

FIGURE 44: TRANSFUSED SEPARATIONS PER 1000 POPULATION, TOTAL AND PRIVATE, BY JURISDICTION, 2008‐09


As will be evident in the discussion below, the level of private sector activity in the blood sector in Queensland stands out on a number of measures. For example, Figure 45 below shows the ratio of private to public separations involving transfusion, on a per bed basis. The capacity in the public sector is higher on a national level and hence a greater proportion of transfused separations would be expected to be generated in the public sector. Adjusting the number of transfused separations for the number of beds in the public and private sectors adjusts for the capacity of the sectors.

Nationally, the number of transfused separations per bed in the private sector was around 93 per cent of that in the public sector. That is, the rate of transfused separations per bed was marginally lower in the private sector than in the public sector. This means that, nationally, there was a slightly higher propensity for public sector separations to be associated with transfusion compared to the private sector. This relationship held for all jurisdictions but Queensland. In Queensland, private sector transfused separations per bed were 165 per cent of that in the public sector. That is, the private sector shows a much greater propensity to transfuse admitted patients than the public sector in that State.

Stakeholders consulted during the project indicated that there has been a growth in private sector activity in the area of haematology oncology in Queensland, with a significant number of private institutions opened in recent years to cater for related treatment. This could be a factor affecting the high rates of use of red cells and IVIg in Queensland in the private sector. However, there was no jurisdictional based data available that could identify private sector volumes of product issues to be able to substantiate this.

‐

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

Separations per 1000 Population

Total

Private

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FIGURE 45: TOTAL TRANSFUSION RELATED SEPARATIONS PER BED, PRIVATE TO PUBLIC RATIO, 2008‐09


Product‐related trends

There were also differences in the public‐private proportions associated with particular blood products. For example, IVIg (Gamma Globulin) transfusions vary significantly, across both jurisdictions and transfusion types. Again, the pattern between public and private sectors in Queensland stands out from the other jurisdictions (Figure 46). Queensland and NT are the only jurisdictions where the rate of IVIg‐related separations per bed is higher in the private sector than in the public sector.

Figure 46 also shows that Victoria, WA and ACT have relatively high rates of IVIg‐related separations per bed in the public sector and overall, for example, significantly higher than in NSW. These data accord with these jurisdictions’ relatively high rates of IVIg transfused separations per population discussed earlier.

0%

20%

40%

60%

80%

100%

120%

140%

160%

180%


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FIGURE 46: SEPARATIONS INVOLVING TRANFUSION OF GAMMA GLOBULIN, PUBLIC AND PRIVATE SECTORS PER BED, 2008‐09


Queensland again went against the national trend in terms of the rate of separations per private sector bed involving transfusion of red cells (Figure 47).

FIGURE 47: SEPARATIONS INVOLVING TRANFUSION OF RED CELLS, PUBLIC AND PRIVATE SECTORS PER BED, 2008‐09


The same relationship was true in Queensland in regard to the private sector and transfusions involving platelets and Other Serum. Nationally, the private sector rate of separations per bed involving transfusion of platelets was 72 per cent of the public rate. In Queensland it was 163 per cent. Nationally, the private sector rate of separations per bed involving Other Serum was 70 per cent of the public rate. In Queensland, the private sector rate was 130 per cent of the public rate. For all the other large jurisdictions, the private to public ratio for other serum was below the national average and in the vicinity of 50 per

‐

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

1.80


Separations per Bed

Overall

Public

Private

‐

0.50

1.00

1.50

2.00

2.50

3.00

3.50


Separations per Bed

Overall

Public

Private

P a g e | 86

cent. (Volumes of both FFP and albumin were growing over this period in Queensland which makes it difficult to determine which of these products might account for the greater proportion of private sector transfused separations in this category.)

As mentioned above, the national split between public and private sectors in terms of total transfused separations has remained stable over the 2003‐04 to 2008‐09 period. However, there are some differences at the individual product level. For example, Table 19 shows that the number of transfusions involving IVIg and also Other Serum have grown at faster rates in the private sector than in the public. Again, it is not possible to separately identify separations involving albumin from those involving FFP in the Other Serum category.

TABLE 19: HOSPITAL SEPARATIONS ASSOCIATED WITH TRANSFUSION, 2003‐04 TO 2008‐09

2003‐04 2007‐08 2008‐09 Growth over Period(a)

Private Public Private Public Private Public Private Public

Exchange Transfusion 331 100 99 (70%)

Tx of Autologous Blood 14,132 1,681 12,402 3,531 13,392 3,549 (5%) 111%

Tx of Blood Expander 1,286 4,502 6,904 3,196 7,834 5,749 509% 28%

Tx of Coagulation Factors 332 4,268 970 6,590 1,219 8,202 267% 92%

Tx of Gamma Globulin 18,154 39,250 29,200 60,582 34,936 68,232 92% 74%

Tx of Leukocytes 30 121 58 99 32 50 7% (59%)

Tx of Other Serum 6,838 31,628 17,219 52,884 21,581 60,626 216% 92%

Tx of Other Substance 904 497 458 578 361 261 (60%) (47%)

Tx of Packed Cells 109,444 234,852 118,200 266,602 119,264 274,852 9% 17%

Tx of Platelets 12,828 32,962 14,668 41,340 15,467 42,222 21% 28%

Tx of Whole Blood 1,556 7,258 1,017 6,109 774 6,093 (50%) (16%)

Total 165,504 357,350 201,096 441,611 214,860 469,935 30% 32%

Note: Parentheses indicate negative values.

Source: National Admitted Patient Care Collection, 2003-04 to 2008-09, Department of Health and Ageing

WHO USES BLOOD AND WHAT IS IT USED FOR IN AUSTRALIA?

DATA LIMITATIONS

In general, data is readily found in the Australian blood sector in regard to product issue at both national and state and territory level. Data also exists within the Blood Service in regard to product issue to individual AHPs. However, data on the end use of blood products within the health system, while collected, is not routinely aggregated and reported. Some studies on the end use of blood products have been conducted as retrospective, specific projects, including Cobain (2007), a red cell utilisation study in NSW and the SA red cell utilisation project (2009) referred to earlier.

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It is understood that all hospitals trace their blood products received through the hospital system to recipient. This traceability is needed for safety and legal requirements, for example, in the case of product recall or batch contamination risk.

Stakeholders consulted explained that this information, under present administrative practice, crosses many separate databases and is not routinely joined up.

WHO USES BLOOD?

A small amount of data was found to be available to indicate general demographic patterns of blood products use in Australia. The general pattern indicated was that the consumption of blood and blood products is positively correlated with age.

In regard to fresh blood products, the Cobain (Ibid.) study of WA data from 2001‐02 found that the older age groups used greater quantities of blood products on a per population basis (Figure 48).

FIGURE 48: PROPORTION OF FRESH BLOOD PRODUCT USE BY AGE GROUP, WA 2001‐02

Source: TJ Cobain, EC Vamvakas, A Wells, K Titlestad ‘A survey of the demographics of blood use’, Transfusion Medicine, 2007, 17, 1-15

The pattern was particularly pronounced for red cells.

This general pattern of use for red cells was supported also in a study using data from a nine month period during 2007‐08 in Victoria (Shortt, 2009). People in the older age groups, particularly over 60 years of age, received a higher number of transfusions than those in the younger age groups.

Unpublished data provided by SA for the period 2006‐07 to 2008‐09 also show, for red cells, the use is positively correlated with age (Figure 49).

0%

10%

20%

30%

40%

50%

60%

<40 years 40‐70 years >70 years

Red cells

Platelets

Plasma

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FIGURE 49: TOTAL AMOUNT OF RED CELL UNITS TRANSFUSED, BY AGE OF RECIPIENT, SA 2006, PUBLIC HOSPITALS

Source: SA Department of Health

In general, older age groups use a greater amount of red cells, although some younger age groups are the major recipients of certain procedures, for example, liver transplants.

IVIg use is also correlated with ageing. In 2009‐10, 69 per cent of patients receiving IVIg were aged over 50 years (Australian Red Cross Blood Service, 2010c).

There was no information available to the project on the demographic profile of the volumes of the other blood products. However, as is in the next section below, many of the conditions for which the products are used correlate positively with age. As well, some information on the age distribution of transfusion of other blood products is available from the hospital separations data.

The hospital separations dataset shows that the proportion of separations involving transfusions (all blood and blood products), correlates positively with the age of patients (Figure 50). The pattern is mirrored in the private sector as well.

6593, 16%

14313, 36%

19218, 48%<40

40‐69

70+

Total: 40124

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FIGURE 50: PERCENTAGE OF SEPARATIONS ASSOCIATED WITH TRANSFUSION, BY AGE OF PATIENT, 2008‐09


Transfusion‐related separations grew in all age categories between 2003‐04 and 2008‐09. However, the strongest growth in transfused separations (all blood and blood products) over the period 2003‐04 to 2008‐09 was in the 40 to 70 year age bracket (Figure 51).

FIGURE 51: PERCENTAGE CHANGE IN SEPARATIONS INVOLVING TRANSFUSION, BY AGE OF PATIENT, 2003‐04 TO 2008‐09


Table 20 shows the number of transfused separations in 2008‐09 according to the main products under discussion in this report. For all products shown in this table, except red cells, the highest proportions of transfused separations nationally were recorded for the 40 to 70 year age group.

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

1,400,000

<40 40 < 70 Over 70

Separations


Tx of Autologous Blood




Tx of Leukocytes

Tx of Other Serum


Tx of Packed Cells

Tx of Platelets

‐

5%

10%

15%

20%

25%

30%

35%

40%

<40 40 < 70 Over 70

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TABLE 20: NUMBER OF TRANSFUSED SEPARATIONS BY BLOOD PRODUCT TYPE AND AGE OF PATIENT, 2008‐09

ACT NSW NT Qld SA Tas Vic WA National

Tx* of Coag’n Factors

32 1361 10 586 351 82 1822 294 4714

<40 13 344 10 244 93 14 587 58 1,443

40 < 70 19 519 261 143 57 719 115 1,889

Over 70 498 81 115 11 516 121 1,382


854 11326 153 15589 3518 669 14322 5108 51584

<40 273 2,625 58 2,530 675 90 2,633 1,288 10,197

40 < 70 470 5,718 85 9,191 2,009 426 8,035 2,868 28,810

Over 70 111 2,983 10 3,868 834 153 3,654 952 12,577

Tx of Other Serum

706 11952 287 7140 2651 673 13297 4325 41105

<40 59 1,707 82 1,317 316 58 1,673 729 5,996

40 < 70 332 5,177 175 3,457 1,040 309 6,360 2,030 18,893

Over 70 315 5,068 30 2,366 1,295 306 5,264 1566 16,216

Tx of Packed Cells

2844 56227 1205 40879 19918 3346 54551 18078 197058

<40 315 6,966 366 5,054 2,044 375 5,667 2,374 23,169

40 < 70 1,127 18,290 609 15,146 6,714 1,189 18,319 6,450 67,846

Over 70 1,402 30,971 230 20,679 11,160 1,782 30,565 9,254 106,043

Tx of Platelets

236 7375 7513 2669 366 7503 3026 28846

<40 33 1,531 1,349 361 52 1,425 511 5,340

40 < 70 137 3,391 3,920 1,436 181 3,560 1,688 14,381

Over 70 66 2,453 2,244 872 133 2,518 827 9,125

*Tx is an abbreviation for ‘transfusion’.


The prominence of the 40 to 70 year age bracket was most stark for transfusion of IVIg (Figure 52).

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FIGURE 52: RELATED SEPARATIONS INVOLVING TRANSFUSION OF GAMMA GLOBULIN, BY AGE GROUP AND JURISDICTION, 2008‐09


Nevertheless, it has been the over 70 age group that has experienced the strongest growth in hospital separations involving transfusion of IVIg (Figure 53).

FIGURE 53: CHANGES IN SEPARATIONS INVOLVING TRANSFUSION OF SELECTED BLOOD PRODUCTS, 2003‐04 TO 2008‐09


This was a common pattern across jurisdictions (Figure 54), although the rates of growth vary significantly. Growth in separations associated with transfusion of IVIg among the over 70s in Queensland and Tasmania stands out.

This may or may not correspond with volume of usage, as the mix of conditions for which IVIg is used involves differing dosage regimes (as was discussed earlier in the report).

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

10,000

<40 Over 70

40 < 70

<40 Over 70

40 < 70

<40 Over 70

40 < 70

<40 Over 70

40 < 70


Separations

‐

20%

40%

60%

80%

100%

120%

140%

160%


Tx of Other Serum

Tx of Packed Cells

Tx of Platelets

Change

<40

40 < 70

Over 70

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FIGURE 54: PERCENTAGE CHANGE IN SEPARATIONS INVOLVING TRANSFUSION OF GAMMA GLOBULIN, BY AGE AND JURISDICTION, 2003‐04 TO 2008‐09


The fastest growth in separations involving ‘other serum’ (including FFP and albumin) was recorded for the 40 to 70 year age group (Figure 53 above). Figure 55 below shows that the growth rate in this age group has been high in first, Victoria, but also Queensland. (While the number of separations involving ‘other serum’ in Tasmania has grown dramatically amongst the under 40s, the small numbers involved mean that this growth is unlikely to have contributed significantly to overall growth in ‘other serum’ transfusions.)

(50%) ‐ 50% 100% 150% 200%

ACT

NSW

NT

Qld

SA

Tas

Vic

WA

Over 70 40 < 70 <40

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FIGURE 55: CHANGES IN SEPARATIONS INVOLVING TRANSFUSION OF ‘OTHER SERUM’, 2003‐04 TO 2008‐09


WHAT ARE BLOOD AND BLOOD PRODUCTS USED FOR?

As mentioned earlier in this report, some of the blood products discussed above have very limited and well defined clinical uses. For example, anti‐D preparations are used to prevent maternal sensitisation and HDNB; the clotting factors and recombinant products are used in the treatment of haemophilia and other bleeding disorders.

Other products, however, have a range of clinical indications. This is true of the fresh blood products, IVIg and albumin. While Prothrombinex‐VF has in one sense a very limited use, that is warfarin reversal, it too is associated with a wide range of clinical cases because of the breadth use of warfarin.

As has been mentioned more generally above, information pertaining to the end use of these blood and blood products in Australia is not readily attainable within the current system. Recent data on the clinical uses of fresh blood products, albumin and Prothrombinex‐VF, in particular, were sparse. The results of data obtained for this project are provided below.

MAIN CLINICAL USES OF FRESH BLOOD PRODUCTS

An NBA report on fresh blood demand drivers (National Blood Authority, 2007) identified several clinical demand drivers for fresh blood products. These included:

incidence of haematological cancers;

(50%) ‐ 50% 100% 150% 200% 250% 300% 350% 400% 450%

ACT

NSW

NT

Qld

SA

Tas

Vic

WA

Change

Over 70 40 < 70 <40

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malignant neoplasms of lymphoid, haematopoietic and related tissue;

diseases of the blood and blood forming organs;

surgical procedures to treat cardiovascular diseases;

surgical procedures more generally.

Red cells

Synthesizing the information from several different sources shows that the main clinical uses for red cells—as measured by greatest proportion of total red cell use—are:

haematology oncology; and

surgical procedures, particularly:

: cardiothoracic surgery;

: orthopaedic procedures, particularly knee and hip replacements;

: organ transplants.

These two broad areas could account for around 50‐60 per cent of total red cell use.

Other main clinical uses include:

gastroenterology and gastrointestinal bleeding;

trauma cases;

obstetrics and gynaecology.

DATA ON CLINICAL USE OF RED CELLS

Cobain study

Data used in the Cobain study referred to above showed that seven clinical areas accounted for close to 80 per cent of total red cell use. These areas are summarised in Table 21.

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TABLE 21: MAJOR CLINICAL USES OF RED CELLS, WESTERN AUSTRALIA, 2001‐02

Treatment area Proportion of total red cell use

Haematology including malignancy 20.70 %

Gastro Intestinal surgery and medical 14.05 %

Orthopaedic surgery 13.80 %

Cardiovascular surgery 10.80 %

Trauma 9.50 %

Renal disease 5.50 %

Obstetrics and gynaecology 5.00 %

Source: TJ Cobain, EC Vamvakas, A Wells, K. Titlestad A survey of the demographics of blood use, Transfusion Medicine, 2007, 17, 1-15

‘Bloodhound’ study

The 2009 ‘Bloodhound’ study (Shortt, 2009) showed the following main clinical uses of red cells:

TABLE 22: MAJOR CLINICALS USES OF RED CELLS, VICTORIA 2007‐08

Clinical Use Percentage of units transfused

Haematology Oncology 34

Surgery 28

Other Medical 13

Obstetrics & Gynaecology 4

Trauma 2

Other/ unknown 19

Source: Shortt et al. (2009), Assessment of the urgency and deferability of transfusion to inform emergency blood planning and triage: the Bloodhound prospective audit of red blood cell use, Transfusion Vol 49, Issue 11

SA unpublished data

The SA unpublished data on red cell usage shows the five procedures recording the highest rates of transfusion episode were as in Table 23.

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TABLE 23: TOP FIVE DIAGNOSIS RELATED GROUPS ACCORDING TO PROPORTION OF ALL SEPARATIONS TRANSFUSED WITH RED CELLS, SOUTH AUSTRALIA, 2006

Diagnosis Related Group Percentage of cases

with transfusion

Units

transfused

Average

units

transfused

per case

A01Z‐Liver Transplant 100 198 13.20

P61Z‐Neonate, < 750 g 97 302 8.39

A08A‐Autologous Bone Marrow Transplant W

Catastrophic

93 223 5.44

CC A07Z‐Allogeneic Bone Marrow Transplant 89 206 12.88

R60A‐Acute Leukaemia W Catastrophic CC 87 566 5.19


These were not necessarily the most common procedures and therefore do not account for the greatest volume of blood use in an overall sense. The procedures found to be responsible for the greatest volume of blood use in this sense were as per the table below. This table echoes the pattern of high blood‐use conditions as the previous studies, including haematology oncology (the leukaemia related DRGs and red blood cell disorders); orthopaedic (the hip and femur procedures); gastrointestinal, including lower intestinal; and cardiac surgery.

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TABLE 24: PROCEDURES WITH GREATEST TOTAL RED CELL USE, SOUTH AUSTRALIA, 2006

Diagnosis Related Group

Units

transfused

Percentage of

cases with

transfusion

Average

units

transfused

per case

A06Z‐Tracheostomy or Ventilation >95 hours 3,795 63% 8.14

Q61C‐Red Blood Cell Disorders W/O Catastrophic

or Severe CC

3,123 36% 2.42

R61C‐Lymphoma and Non‐Acute Leukaemia,

Sameday

2,029 44% 2.20

I08A‐Other Hip and Femur Procedures W

Catastrophic or Severe CC ]\

854 59% 2.73

G46A‐Complex Gastroscopy W Catastrophic or

Severe CC

749 55% 3.92

G02A‐Major Small and Large Bowel Procedures W

Catastrophic CC

681 51% 3.57

R61B‐Lymphoma and Non‐Acute Leukaemia W/O

Catastrophic CC

655 33% 2.68

G42A‐Other Gastroscopy for Major Digestive

Disease

647 40% 3.17

I03B‐Hip Replacement W Cat or Sev CC or Hip

Revision W/O Cat or Sev CC

631 44% 2.74

R60B‐Acute Leukaemia W Severe CC 621 69% 2.34

F06A‐Coronary Bypass W/O Invasive Cardiac Inves

W Catastrophic or Severe CC

594 63% 2.98

Q60A‐Reticuloendothelial and Immunity Disorders

W Catastrophic or Severe CC

574 54% 3.15

Q61B‐Red Blood Cell Disorders W Severe CC 571 65% 2.84

R60A‐Acute Leukaemia W Catastrophic CC 566 87% 5.19


PLATELETS

Less information was available to indicate clinical end use for platelet products.

The Cobain study (2007) included a breakdown of the clinical uses for platelets. Haematology and cardiovascular surgery together account for more than 55 per cent of platelet use.

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TABLE 25: MAJOR CLINICAL USES OF PLATELETS, WESTERN AUSTRALIA, 2001‐02

Treatment area Proportion of total platelet use (per cent)

Haematology 34

Cardiovascular surgery 21.6

Trauma 13.0

Bone marrow transplantation 6.7


FRESH FROZEN PLASMA

Again, little information was available to indicate clinical end use for FFP. Cobain’s study included a breakdown of clinical uses for FFP. Trauma accounts for the highest use, although is closely followed by use in cardiovascular surgery.

TABLE 26: MAJOR CLINICAL USES OF FRESH FROZEN PLASMA, WESTERN AUSTRALIA, 2001‐02

Treatment area Proportion of FFP use (per cent)

Trauma 26.6

Cardiovascular surgery 23.0

Gastro Intestinal surgery 11.5

Other orthopaedic surgery 6.1

Haematology 5.2

Hepatic/biliary 5.2


While not directly comparable, more recent data, from a clinical audit of FFP use in Victoria, Tasmania and ACT hospitals in 2008 showed the major reasons for use of FFP are indicated in Table 27.

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TABLE 27: MAJOR CLINICAL USES OF FRESH FROZEN PLASMA—VICTORIA, ACT, TASMANIA, 2008

Diagnosis criteria Proportion of FFP transfusion

episodes21(per cent)

Abnormal coagulation and active blood loss 56

Abnormal coagulation and invasive

procedure/surgery

45

Warfarin effect 26

Liver disease/failure 16

Following cardiac bypass 14

Acute DIC 3

TTP 2

Other 1

Source: Clinical audit of fresh frozen plasma use in Victorian, Tasmanian and ACT hospitals: 2008, Victorian Government Department of Human Services, 2008

MAIN CLINICAL USES FOR PLASMA DERIVED PRODUCTS

The main products of concern are IVIg, albumin and Prothrombinex‐VF, as they are the products with the widest range of uses. As has been mentioned previously, the other plasma‐derived products have much narrower recipient bases. However, data providing a breakdown of the clinical uses associated with albumin and Prothrombinex‐VF were not available to this project. The discussion below pertains consequently to IVIg only.

Intravenous Immunoglobulin

Five disease groups account for almost 70 per cent of IVIg issued in 2009‐10 (Australian Red Cross Blood Service, 2010d). These are:

21 One transfusion episode may have been assigned one or more diagnosis criteria, therefore the sum of all diagnoses may exceed 100%.

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TABLE 28: MAJOR CLINICAL USES OF IVIG, 2009‐10

Condition Percentage use

Acquired hypogammaglobulinemia secondary to haematological malignancy 20.6

Chronic inflammatory demyelinating polyneuropathy (CIDP) 20.5

Primary immune deficiency 16.1

Myasthenia Gravis (MG) 6.3

Multifocal motor neuropathy (MMN) 5.9

Total 69.4

Source: ARCBS Intravenous Immunoglobulin Use in Australia, August 2010

CLINICAL USE AND AGEING

As was discussed in the previous section, there are several studies, which indicate that red cell use is positively correlated with ageing. Haematological cancers, associated with over 20 per cent of IVIg use in Australia in 2009‐10, are also correlated with age. Taking ageing into account, the Blood Service projects IVIg demand to grow by around 276 per cent over the 2010‐11 base year to 2019‐20.

HOW DOES BLOOD USE IN AUSTRALIA COMPARE INTERNATIONALLY?

Data enabling international comparisons of blood and blood product use were also very sparse and in most instances quite dated. What data were available showed that Australian use of red cells ranks towards the lower end of most countries. On the other hand however, use of IVIg in Australia was comparatively high.


Australia’s volume of red cells has ranged between 36.4 and 37.7 issues per 1000 population over the period since NBA was established.

Red cell usage per 1000 population in 2003 is shown for a select number of Council of Europe member countries below22. Australia’s usage rate was at the bottom of this range, close to that of Netherlands and Norway at this time.

22 Countries with a high human development index (HHDI)

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TABLE 29: RED CELL USE PER 1000 POPULATION FOR SELECTED COUNTRIES, 2003

Country Red cell use (units) per 1,000 inhabitants

Denmark 70.8

Germany 50.2

Netherlands 37.6

Norway 37.6

Sweden 49.7

Switzerland 42.7

UK 43.7

Australia 37.1

Source: Council of Europe, ‘The collection, testing and use of blood and blood products in Europe, 2003’

Data provided on a confidential basis to NBA from material held by the Council of Europe shows an update on this red cell usage for 200523.

23 Figures relating to 2005 may not have been ratified by the relevant country.

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FIGURE 56: RED CELL USE PER 1000 INHABITANTS, SELECTED EUROPEAN COUNTRIE

Source: National Blood Authority, Monograph Series 05 Whole Blood and Red Cell Products 2010 p.37.

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There are many European countries with red cell usage rates above and even well above that of Australia.

More recent data was available to compare usage rates per population for Canada (excluding Quebec24) and NZ. These countries both recorded lower rates of use than Australia (Table 30).

TABLE 30: RED CELL USE PER 1000 POPULATION, AUSTRALIA, CANADA AND NEW ZEALAND, 2007‐08 TO 2009‐10

Country 2007‐08 2008‐09 2009‐10

Canada(a) 31.68 32.58 na

New Zealand 33.23 33.10 32.63

Australia 36.64 37.08 36.39

(a) Area of Canada covered by Canadian Blood Services, that is Canada except Quebec.

Sources: Canadian Blood Services Annual Reports 2007-08, 2008-09, 2009-10; Statistics Canada, http://www40.statcan.gc.ca/l01/cst01/demo02a-eng.htm;New Zealand Blood Service Annual Report 2009/10, Statistics New Zealand, http://www.stats.govt.nz/browse_for_stats/population/estimates_and_projections/NationalPopulationEstimates_HOTPSep08qtr.aspx; NBA National Supply Plan and Budget

Data from Canada (excluding Quebec) and New Zealand also indicated that Australia’s use of FFP and platelets was relatively higher (Table 31).

TABLE 31: PLATELET AND FFP USE PER 1000 POPULATION, AUSTRALIA, CANADA AND NEW ZEALAND, 2007‐08 TO 2009‐10

Country 2007‐08 2008‐09 2009‐10

Platelets FFP Platelets FFP Platelets FFP

Canada(a) 4.1 2.2 4.2 2.3 4.3 2.2

New Zealand 4.0 4.8 4.5 4.7 4.5 4.8

Australia 5.6 6.9 5.5 7.1 5.9 7.4

(a) Area of Canada covered by Canadian Blood Services, that is Canada except Quebec.

Sources: Canadian Blood Services Annual Reports 2007-08, 2008-09, 2009-10; Statistics Canada, http://www40.statcan.gc.ca/l01/cst01/demo02a-eng.htm;New Zealand Blood Service Annual Report 2009/10, Statistics New Zealand, http://www.stats.govt.nz/browse_for_stats/population/estimates_and_projections/NationalPopulationEstimates_HOTPSep08qtr.aspx; NBA National Supply Plan and Budget

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No information was found to indicate usage rates of Prothrombinex‐VF or albumin in comparable countries.


The use of IVIg in Australia is high in relation to comparable countries. Estimates for 2009‐10, on a population basis, are contained in Table 32.

TABLE 32: IVIG VOLUMES PER 1000 POPULATION, SELECTED COUNTRIES, 2010

Country Estimated IVIg use rate (g/1000 population)

USA 127

Canada 112

Australia 121

France 73

New Zealand 60

UK 50

Germany 32

Source: CSL Ltd Presentation to SRG Ltd, September 2010, which cites various sources for this data and information (CSL, NBA, ARCBS, CSL estimates, MRB and PPTA).

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Cost of Blood and Blood Products

What are the ‘Costs’ Of Blood In Australia?

This report examines several aspects of cost in relation to blood and blood products in Australia. These include:

the direct financial costs of blood and blood products as borne by the Australian Government and the states and territories; also referred to as ‘costs to budget’ or ‘the product cost of supply of blood and blood products’;

the indirect financial costs of administering blood, including the ‘transfusion on‐costs’ (also called ‘in‐hospital transfusion costs’) and other budgetary items associated with blood and blood product supply and administration;

the full economic cost of supplying and administering blood and blood products, that is the explicit and non‐explicit financial costs as well as other socio economic costs.

The report also identifies and examines cost drivers in the Australian blood sector.

DATA FOR ANALYSIS

The main source of data for the analysis of costs to budget was the NBA National Supply Plan and Budget data. The National Supply Plan and Budget (NSPB) contains the cost to all Australian governments (that is, Commonwealth and jurisdictions) for the product cost of supply of blood and blood products, as well as some additional costs. It identifies these costs of supply for each state and territory. The analysis below does not separately identify the jurisdictional and Commonwealth expenditure contribution amounts, but rather concentrates on the total blood budget for each state and territory. Unless otherwise specified, the analysis pertains to the product cost of supply of all blood and blood products on the NSPB, excluding diagnostic blood products.

Blood and blood product prices are national prices. For the period 2003‐04 to 2009‐10, blood and blood product prices in this report were derived from total product expenditure divided by total volume.

EXPLICIT COSTS – THE ‘COSTS TO BUDGET’

OVERVIEW

The costs to budget of blood and blood products have been rising, and rising steeply, in recent years. Growth of the total spending on the product cost of blood and blood products25 (all Australian governments) averaged approximately 12 per cent per annum for the period 2003‐04 to 2009‐10 (Table 3, p20). In 2010‐11, the total budgetary cost is estimated to be $937 million, which will represent an increase again of approximately 10 per cent over 2009‐10.

25 Relates to expenditure on blood and blood products, that is, does not include other related costs in the system such as departmental expenses and other budgetary items.

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TABLE 33: NATIONAL BLOOD BUDGET BY MAJOR PRODUCT GROUP, 2003‐04 TO 2009‐10

Fresh Blood Products

$ million

Plasma derived products

$ million

Recombinant Products

$ million

Total

$ million

2003‐04 242.1 151.6 48.6 442.3

2004‐05 269.3 141.7 81.6 492.6

2005‐06 297.0 140.6 106.9 544.5

2006‐07 331.2 164.8 119.2 615.2

2007‐08 359.6 193.1 126.0 678.8

2008‐09 414.8 220.4 136.2 771.4

2009‐10 451.4 246.8 152.8 850.9

Source: National Supply Plan and Budget, 2003-04 to 2009-10, NBA

Fresh blood products accounted for over half of the total national blood product supply cost in 2009‐10 (Figure 57). The product supply cost of fresh blood products has traditionally made up the bulk of the total product cost of the blood supply. However, product expenditure on fresh blood products taken as classified in the NSPB includes expenditure on Plasma for Fractionation (PfF). This is an intermediate good used in the production of plasma‐derived products. Inclusion of this product under fresh blood products distorts the breakdown of the national blood budget. Expenditure on fresh products, which are directly consumed, is overstated, while expenditure on plasma derived products is understated. If PfF were removed from the fresh products total in 2009‐10, expenditure on consumable fresh products would fall to 47 per cent of the national cost of supply of blood and blood products.

As classified in the National Supply Plan and Budget, national expenditure on the product supply cost of plasma derived products accounted for 29 per cent of the total product cost of the blood supply in 2009‐10 and recombinant products 18 per cent (Figure 57).

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FIGURE 57: RELATIVE PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, 2009‐10.


Expenditure on the product cost of supply of recombinant products increased relatively early in the period 2003‐04 to 2009‐10. For the last five years, however, the relative proportions of the three main product groupings have remained largely the same in the national blood budget (Figure 58).

FIGURE 58: TOTAL PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, 2003‐04 TO 2009‐10, BY MAJOR PRODUCT GROUP


Prices for blood and blood products in Australia are national prices. Hence differences at jurisdictional level follow patterns of demand (use).

53%

29%

18%

Fresh

Plasma Derived

Recombinant

Total: $851 million

‐

100.0

200.0

300.0

400.0

500.0

600.0

700.0

800.0

900.0

$ m

illion

Recombinant Products

Plasma derived products

Fresh Blood Products

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At the jurisdiction level, total product costs of blood and blood product supply are driven by population numbers (Figure 59). The relative proportions of fresh, plasma derived and recombinant products have generally mirrored the national breakdown over the period.

FIGURE 59: TOTAL PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY MAJOR PRODUCT GROUP, BY STATE AND TERRITORY, 2009‐10


Significant cost trends within the major blood product groupings include:

among the fresh blood products, a rise in expenditure on red cells and platelets above the rates of growth in volume, reflecting rising average prices for these products;

among the plasma derived group:

total expenditure dominated by expenditure on IVIg, which has risen strongly over the period since 2003‐04, due mainly to growth in demand;

a steep rise in expenditure on clotting factors since 2006‐07, driven mainly by expenditure on Prothrombinex‐VF;

for the recombinant products, a significant rise in expenditure on Recombinant Factor VIII (rFVIII);

a significant rise in the cost per capita for blood and blood products overall, but with variations in the pattern for individual products.


National Trends

While fresh blood products account for the majority of the total product cost of supply of blood and blood products, red cells account for the major proportion of the costs of fresh blood products (Figure 60).

0

50

100

150

200

250

300

ACT NSW NT QLD SA TAS VIC WA

$ Millions

Recombinant

Plasma Derived

Fresh

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FIGURE 60: TOTAL PRODUCT COST OF SUPPLY OF FRESH BLOOD PRODUCTS, BY PRODUCT GROUP(a), 2009‐10

(a) Up until the end of 2009‐10, ARCBS was paid on a grant basis, which included a separate allocation for capital expenses. Capital is consequently included above as a separate category among fresh blood product costs. From 2010‐11, capital was attributed to individual product prices.


The most notable trend in expenditure on red cells is that it has grown by around 11 per cent per year over the period 2003‐04 to 2009‐10 (Table 34), contrasting with growth in volume of just over 1 per cent for the same period. The driver for growth in expenditure on red cells has come from price. There has been a move over the period towards the more expensive leucodepleted red cells. In 2003‐04 the leucodepleted red cells made up just 7 per cent of total red cell volume. This percentage has increased each year and by 2007‐08 had risen to almost 28 per cent. In 2008, the policy decision was taken to move red blood cell supply to 100 per cent leucodepleted in the interests of patient safety. As a result, 86.5 per cent of the red cells supplied in 2008‐09 were leucodepleted, and by 2009‐10, this had become 100 per cent of the total red cell volume.

Now that the red cell supply has reached 100 per cent leucodepleted, from here forward the growth rate in expenditure should mainly reflect volume increases and planned price increases. That is, the rise in expenditure should become less steep, barring any shocks to the price of production.

0%

55%

11%2%

1%

0%

0%

22%

9%

Whole Blood

Red Cell Products

Platelet Products

FFP Products

Cryoprecipitate

Cryo‐depleted Plasma

Other Fresh Products

Plasma for Fractionation

Capital

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TABLE 34: TOTAL PRODUCT COST OF SUPPLY OF FRESH BLOOD PRODUCTS, 2003‐04 TO 2009‐10

Product 2003‐04

$ million

2004‐05

$ million

2005‐06

$ million

2006‐07

$ million

2007‐08

$ million

2008‐09

$ million

2009‐10

$ million

Red cell products 133.7 149.2 161.3 178.8 201.4 234.9 246.5

Platelets (pooled) 16.4 18.5 26.6 25.6 17.1 20.6 23.8

Platelets –

apheresis

9.9 12.5 16.3 20.3 24.7 25.3 26.3

FFP (whole blood

derived)

5.0 5.5 5.9 6.0 5.9 7.3 7.6

FFP – apheresis 0.0 0.0 0.2 1.1 1.5 1.2 1.3

Plasma for

Fraction’n

52.2 55.7 58.7 65.9 70.6 81.7 97.4

Other fresh

products

3.0 3.3 4.0 4.1 5.8 6.2 7.2

ARCBS Capital

component

22.0 24.5 27.0 29.6 32.6 37.6 41.2

Total 242.1 269.3 297.0 331.2 359.6 414.8 451.4


There has been a similar trend in expenditure on platelet products as a whole. While platelet volume grew by about 4.7 per cent per annum over the period, expenditure has grown by approximately 11 per cent per annum. This reflects the increase in the average price of platelet products with increasing use of the more expensive apheresis platelets. Expenditure on apheresis platelets increased by over 166 per cent over the period, as compared with around only 46 per cent growth for pooled platelets.

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FIGURE 61: TOTAL PRODUCT COST OF SUPPLY OF SELECTED(a) FRESH BLOOD PRODUCTS, 2003‐04 TO 2009‐10(b)

(a) These products accounted for over 99 per cent of expenditure on fresh blood products in 2009‐10. (b) Up until the end of 2009‐10, ARCBS was paid on a grant basis, which included a separate allocation for capital expenses. Capital is consequently included above as a separate category among fresh blood product costs. From 2010‐11, capital was attributed to individual product prices.


State and Territory Trends

Overall, the trends in the total product costs of supply for fresh blood products by jurisdiction have mirrored the national trend (Figure 62).

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2003‐04 2004‐05 2005‐06 2006‐07 2007‐08 2008‐09 2009‐10

$ m

illion

Red Cells

Platelets

PfF

FFP

Cryoprecipitate

Cryo plasma depleted

Capital

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FIGURE 62: TOTAL PRODUCT COST OF SUPPLY OF FRESH BLOOD PRODUCTS, 2003‐04 TO 2009‐10, BY STATE AND TERRITORY


The trend in national spending per capita on fresh blood products also follows the general upward trend of total expenditure, and is reasonably consistent for all states and territories (Figure 63). WA shows a small deviation from the trend in 2008‐09.

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FIGURE 63: TOTAL PRODUCT COST OF SUPPLY PER CAPITA FOR FRESH BLOOD PRODUCTS, 2003‐04 TO 2009‐10, BY STATE AND TERRITORY



National Trends

There are a few marked trends in the national product cost of supply of plasma‐derived products over the period since 2003‐04:

total cost is dominated by IVIg (Figure 64). This has risen steeply, especially over the period since 2005‐06. This has been mainly driven by rising demand. Price has also risen (see Prices of Blood Products, p.126), but at a lower rate than for total cost;

there has been positive growth in the cost of clotting factors since 2005‐06. This growth can be attributed mainly to FEIBA26, Biostate 500 IU (plasma derived FVIII). Again, growth in these products has been the result mainly of demand, rather than price movements;

there was a significant dip in the costs of several plasma derived products in 2005‐06, particularly the clotting factors, albumin and the hyperimmune products:

26 Factor Eight Inhibitor Bypass Agent (FEIBA)

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: price for albumin (as a group) dropped in 2005‐06, while demand continued to rise (see Prices of Blood Products, p126);

: the volume of Factor VIII (Biostate) in particular, but also Factor IX (MonoFIX) declined dramatically in this year, as recombinant products began to be substituted.

FIGURE 64: TOTAL PRODUCT COST OF SUPPLY OF SELECTED PLASMA DERIVED PRODUCTS, 2003‐04 TO 2009‐10


Jurisdictional trends

The product supply cost patterns over the period for the states and territories generally follow the national trend for plasma‐derived products.

The strong rate of growth of total expenditure on plasma derived products in Queensland, Victoria and NSW is evident from Figure 65. The main driver in Queensland and NSW has been IVIg, and in Victoria, Prothrombinex‐VF.

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FIGURE 65: TOTAL PRODUCT COST OF SUPPLY OF PLASMA DERIVED PRODUCTS BY STATE AND TERRITORY, 2003‐04 TO 2009‐10



National Trends

Total product cost of supply of recombinant products is driven by the cost of rFVIII (Table 35). Figure 66 below shows that expenditure on this product has been rising in absolute terms and also as a proportion of total recombinant expenditure.

TABLE 35: TOTAL COST OF SUPPLY OF RECOMBINANT PRODUCTS, 2003‐04 TO 2009‐10

Product 2003‐04

$ million

2004‐05

$ million

2005‐06

$ million

2006‐07

$ million

2007‐08

$ million

2008‐09

$ million

2009‐10

$ million

Novoseven

(rFVIIa)

14.6 18.8 23.4 27.0 17.4 17.4 26.4

rFVIII 28.5 51.9 67.6 76.7 88.5 94.3 100.7

BeneFIX (rFIX) 5.5 10.9 15.9 15.5 20.1 24.4 25.6

Total 48.6 81.6 106.9 119.2 126.0 136.2 152.8


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FIGURE 66: TOTAL PRODUCT COST OF SUPPLY OF RECOMBINANT PRODUCTS, 2003‐04 TO 2009‐10


Recombinant FVIII has replaced much of the use of plasma derived FVIII.

The growth in price has been comparatively flat (see Prices of Blood Products, p.126).

Jurisdictional Trends

The patterns of product costs of supply of recombinant products per jurisdiction follow the highly individualised usage patterns. In general, the trend for the large jurisdictions in total product supply cost has been upwards, with some variability in the rates of growth from year to year (Figure 67).

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FIGURE 67: TOTAL PRODUCT COST OF SUPPLY OF RECOMBINANT PRODUCTS BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


The growth in cost of rFVIII can mainly be attributed to growth in demand in NSW (Figure 68).

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FIGURE 68: TOTAL PRODUCT COST OF SUPPLY OF RECOMBINANT FVIII, BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


Expenditure on rFVIIa has been very variable, consistent with variations in demand on a small patient base.

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FIGURE 69: PRODUCT COST OF SUPPLY OF RFVIIA (NOVOSEVEN), BY STATE AND TERRITORY, 2003‐04 TO 2009‐10


TRENDS IN COSTS PER CAPITA

As a whole, the product cost of supply of blood and blood products per capita has risen significantly throughout the period since 2003‐04. Table 36 shows that the total cost per capita grew by 75 per cent over the 2003‐04 base, or close to 10 per cent per annum.

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TABLE 36: TOTAL PRODUCT COST OF THE SUPPLY OF BLOOD AND BLOOD PRODUCTS PER CAPITA, 2003‐04 TO 2009‐10

Product 2003‐04

$

2004‐05

$

2005‐06

$

2006‐07

$

2007‐08

$

2008‐09

$

2009‐10

$

Fresh Blood

Products

12.20 13.41 14.61 16.05 17.14 19.39 20.64

Red Cells 6.74 7.43 7.93 8.66 9.60 10.98 11.27

Plasma Derived

group

7.64 7.06 6.92 7.99 9.20 10.30 11.29

Albumin (group) 1.34 1.33 0.53 0.59 0.64 0.69 0.96

Prothrombinex‐VF 0.13 0.19 0.26 0.33 0.42 0.53 0.37

IVIg (domestic &

imported)

3.64 3.69 4.89 5.56 6.36 7.28 8.06

Recombinant

Products group

2.45 4.06 5.26 5.78 6.01 6.36 6.99

All blood & blood

products

22.29 24.53 26.78 29.81 32.35 36.06 38.91


There are variations, however, in the per capita costs of individual products. The movements reflect a combination of effects of growth in volumes and movements in prices. For example, this was seen above in the case of red cells and platelets.

Per capita costs for the plasma‐derived group of products as a whole have also risen. This is mostly accounted for by the rise in the per capita cost for IVIg. The per capita cost of albumin has actually declined. This again is a price effect, as it was shown earlier ‐ volumes of albumin have been steadily rising over the period.

NON‐EXPLICIT FINANCIAL COSTS – THE ‘TRANSFUSION ON‐COSTS’

The cost to governments for the supply and use of blood and blood products extends beyond the explicit ‘cost to budget’.

The first area of indirect cost to government is that of transfusion on‐costs, that is, the costs incurred in the health provider (mainly hospital) setting. These costs are borne by hospital budgets, and ultimately by state and territory governments, with the Australian Government also bearing an indirect impact in its transfers to the jurisdictions. In the Council of Australian Governments agreement on National Health Reform, February 2011, the Australian Government undertook to increase its contribution to efficient growth funding for hospitals to 45 per cent from 1 July 2014, and further to 50 per cent from 1 July 2017. This

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contribution to growth funding would be in addition to the Australian Government’s contribution to base funding.

The process cost of administering the transfusion within the hospital may be 2 to 5 times that of the product cost (Shander, 2010). A recent Australian study demonstrated that the cost of transfusion of a single unit of red cells, including acquisition costs, was about AU$70027 (Thomson, 2009). If all transfusion related costs are calculated, including short‐term and suspected mid and long‐term adverse effects, the total cost of red cell transfusion may represent up to 5 per cent of the total public healthcare budget of some high‐human‐development‐index (HHDI) countries (Shander, 2010).

Activity‐based transfusion cost analyses have been conducted to capture the total resource consumption of all transfusion related processes in the surgical setting of four institutions, two in the US and two in Europe (Shander, 2010). Results showed that more than 30 main processes and several support processes are required within hospitals to deliver transfusion services. These processes include ordering, shipping, receiving, storing, multiple laboratory services, pre‐transfusion examinations, clerical routines, administering and monitoring transfusions, treating adverse transfusion reactions, and others. Clerks, couriers, medical technicians, nurses, assistants, anaesthesiologists, surgeons, haematologists, risk managers, administrators and other personnel are involved in more than 300 resource consuming process steps. Some processes occurred more frequently than the actual number of transfusions administered, because more transfusions were prepared than given.

All major process steps, staff, and consumables to provide RBC transfusions to surgical patients, including usage frequencies, and direct and indirect overhead costs contributed to per‐RBC‐unit costs between $US522 and $US1183 (mean, $US761± $US294). These exceed previously reported estimates (Cantor, 1998; Cremieux, 2000) and were 3.2 to 4.8‐fold higher than blood product acquisition costs.

By multiplying the mean local transfusion rates per transfused surgical patient of the participating hospitals, the mean transfusion related cost per patient varied between $US3,500 and slightly more than $US2,000. Europe (Shander, 2010) (Figure 70).

27 This figure is drawn from unpublished data and quoted from a secondary source. The study was conducted in 2009 and hence it is assumed that the $700 figure relates to 2009 prices.

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FIGURE 70: ACTIVITY BASED COSTS OF TRANSFUSION, SELECTED US AND EUROPEAN HOSPITALS

Source: Reproduced from Shander et al., Activity-Based Costs of Blood Transfusions in Surgical Patients at Four Hospitals, Transfusion Vol. 50, April 2010

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The recognition and quantification of transfusion on‐costs may have implications for cost‐effectiveness analyses, which compare transfusion to other treatment modalities, for example in the case of the treatment of iron deficiency anaemia.

There are a number of other costs to governments associated with the supply and administration of blood and blood products. The major items include:

MBS items related to the administration of blood and bone marrow and also to pathology functions performed, such as blood grouping, which are performed in the private health care setting;

the Australian Government also incurs expenses on the Veterans’ Affairs budget in relation to these items in regard to relevant patients cared for in both public and private settings. However, data indicating the level of expenditure involved were not able to be sourced in the timeframe for this project;

departmental expenses (that is, administrative budget) of NBA;

departmental expenses incurred by the Australian DOHA and state and territory Health authorities in the policy and management functions for the blood sector, as well as blood management initiatives and improvement programs.

The MBS item expenditures are variable costs, that is, they vary with the amount of blood and blood products used. The expenses related to government administration of the sector would be, in majority, in the nature of fixed costs, that is, largely unchanged on the basis of the amount blood and blood products issued in Australia.

Precise estimates for these other costs to budget were not universally obtained for this project. The information in Table 37, however, is indicative of the order of magnitude of the main MBS additional costs. In 2009‐10, MBS blood related expenditures reached more than $43 million.

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TABLE 37: EXPENDITURE ON MEDICARE BENEFITS SCHEDULE ITEMS ASSOCIATED WITH ADMINISTRATION OF BLOOD AND BLOOD PRODUCTS, 2009‐10

MBS Item

no. Brief description

Schedule Fee

($)

2009‐10

Expenditure

($ million)

13706 Admin of blood or bone marrow already

collected. Payable for the transfusion of blood, or

platelets or white blood cells or bone marrow or

gamma globulins

78.80 6.115

65090 Blood grouping (including back‐grouping if

performed) ‐ ABO and Rh (D antigen)

11.20 1.057

65096 Blood grouping (including back‐grouping if

performed), and examination of serum for Rh and

other blood group antibodies, including: (a)

identification and quantitation of any antibodies

detected; and (b) (if performed) any test

described in item 65060 or 65070

41.30 22.205

65099 Compatibility tests by cross match ‐ all tests

performed on any one day for up to 6 units,

including: (a)all grouping checks of the patient

and donor; and (b)examination for antibodies,

and if necessary identification of any antibodies

detected; and (c)(if performed) any tests

described in item 65060, 65070, 65090 or 65096.

(Item is subject to rule 5)

109.65 6.078

65105 Compatibility testing using at least a 3 cell panel

and issue of red cells for transfusion ‐ all tests

performed on any one day for up to 6 units,

including: (a) all grouping checks of the patient

and donor; and (b) examination for antibodies

and, if necessary, identification of any antibodies

detected; and (c) (if performed) any tests

described in item 65060, 65070, 65090 or 65096.

(Item is subject to rule 5)

109.65 7.662

Total 43.283

Source: https://www.medicareaustralia.gov.au/statistics/

The operational costs of NBA totalled approximately $9 million in 2009‐10 Table 4) .

Cost estimates for Australian and state and territory government departmental expenses were note obtained for this report.

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FULL ECONOMIC COST

The full economic cost of supplying and administering blood and blood products is the explicit and non‐explicit financial costs as well as other socio economic costs. There have been a number of international studies, which have attempted to estimate some of the socio‐economic costs of transfusion, for example, the cost of adverse events and sub‐optimal patient outcomes.

For example, a very large retrospective cohort study in 2004 in the US, Morton, et al. (2010) assessed frequency and outcomes associated with blood products transfusion. The study found that average length of stay (LOS) in hospital was 2.5 days longer, and total charges were $US17, 194 higher for the study’s transfused cohort (P less than .0001). In addition, the chances of death were 1.7 times higher (P < .0001) and odds of infection 1.9 times higher (P less than .0001) for the transfused cohort. The study used data from the 2004 Nationwide Inpatient Sample database and measured LOS, postoperative infections (PI), non‐infectious transfusion‐related complications, in‐hospital mortality, and total charges for transfused and non‐transfused cohorts.

Results of many other studies which have indicated increased morbidity following transfusion are referred to in the section on ‘Best practice—appropriate use’ of blood and blood products below.

COST DRIVERS

In this section, the focus of analysis is on the factors that have underpinned recent historical trends in the product cost of supply of blood and blood products.

Cost drivers have come from both supply side and demand side pressures.

SUPPLY SIDE COST DRIVERS

Manufacturing Costs

Information on the manufacturing costs of fresh blood was available through the work done by the NBA on an output‐based funding model (OBFM) for the Blood Service. The OBFM will underpin the structure of prices for fresh blood products supplied under the National Supply Plan and Budget and is discussed in more detail in the Future Trends section of this report.

The highest proportion of total fresh blood manufacturing costs is attributable to ‘donor services’, which includes donor marketing and collection of blood—around 60 per cent (Figure 71). Of this, the collection costs compose the bulk of costs (more than 80 per cent).

The next highest cost component is testing, which represents about one quarter of total manufacturing cost.

Actual production of the fresh blood products and the cost of distribution respectively account for the minor proportions of the total manufacturing process, at around 7 per cent each.

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FIGURE 71: BREAKDOWN OF MAJOR COMPONENTS OF MANUFACTURING COSTS FOR FRESH BLOOD PRODUCTS

Source: Cost Attribution Rules for the ARCBS Output Based Funding Model, NBA

THE COSTS OF SAFETY MEASURES

Ensuring that the blood supply is safe from infectious diseases is a significant driver for costs to budget for blood and blood products. As indicated above, testing represents around one‐quarter of the cost of manufacture of fresh blood products in Australia.

Safety measures can be, at the same time, significant drivers of cost savings if the full economic costs are considered. It is most usual, however, for these savings to be made in ‘non‐explicit’ costs to budget, or in the difficult to quantify area of socio‐economic costs. For example, the business case for the introduction of leucodepletion of red cells and platelets in Australia factored in expected savings of over $5 million to the healthcare system from the removal of the need for the practice of bedside filtration (Australian Red Cross Blood Service, Undated). The capital costs of implementation of 100 per cent leucodepletion, on the other hand, were explicit in the blood budget at around $1 million.

Because of the impact through the supply chain, safety measures continue to put an upward pressure on the prices for blood products, particularly fresh blood products.

Prices of Blood Products

For fresh blood products, which are manufactured and supplied by the Blood Service on a not for profit basis, the product prices reflect the Blood Service costs of production.

As was noted earlier, expenditure on fresh blood products has been rising faster than demand. Figure 72 shows the upward movement over recent years in the average prices28

28 ‘Average price’ is the average for the individual products in each product group, eg the average

price of red cells is equivalent to the average cost of all red cell units supplied, this includes all

Donor Marketing & Collection

Testing

Production

Distribution

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for the major fresh blood products, namely red cells, platelets and FFP. The upturn in the trend for the average price of red cells from 2007 reflects the policy decision taken early in that year to move the red cell supply to 100 per cent leucodepleted. This was largely achieved by then end of 2007‐08. Leucodepleted red cells cost more to produce and have attracted a higher price.



(a) Prices are per the following units: Albumin per 10g; IVIg per gram; other products are standard units. IVIg(D) represents domestically produced IVIg; IVIg(M) represents the pooled average of the two brands of imported IVIg products.

Plasma derived products supplied by CSL and pharmaceutical companies are priced on commercial principles. NBA is a monopsony buyer in the Australian market and should therefore hold a significant degree of market power. However, CSL is also a monopoly supplier in terms of many products. In addition, the market power of CSL is enhanced by the explicit objective within the National Blood Agreement for national self‐sufficiency in blood and blood product supply. Additionally, CSL is a global company and the Australian market is a relatively small one internationally.

In terms of internationally sourced plasma derived, and recombinant, products, Australia is a price taker.

Figure 72 above shows the recent historical pattern in the prices for the plasma‐derived products in focus for this report. Of interest are the falls in price for Prothrombinex‐VF in the current financial year and for albumin (average price for the albumin group of products)

individual red cell products: red cells described as whole blood, leucodepleted, buffy coat poor, paediatric, washed, leucodepleted‐washed, or apheresis.

$0.00

$50.00

$100.00

$150.00

$200.00

$250.00

$300.00

$350.00

$400.00

$450.00

$500.00

Platelets

Red Cells

FFP

Fractionation

Albumin

PTX

IVIg (D)

IVIg (M)

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in 2005‐06. These price declines are coupled with continued increasing demand for these products. Hence the drop in national expenditure on albumin seen above has been a price, not demand, effect. In the case of Prothrombinex‐VF the impact of price is not anticipated to outweigh the effect of overall demand and hence total expenditure is still expected to rise. The fall in the price of Prothrombinex‐VF results from a new plasma product agreement with CSL, which commenced in 2010‐11 (CSL Domestic Fractionation Agreement). Under this agreement the price of Prothrombinex‐VF dropped by 40 per cent from the previous price (National Blood Authority, 2010).

Also of interest is the dramatic fall in the price of overseas sourced IVIg, in stark contrast to the very steady upward trend in the price of domestic manufactured IVIg.

Figure 73 reproduces Figure 72 and includes the price pattern for rFVIIa relative to the other product prices. The very high, and rising, price per unit for the imported rFVIIa is evident.



(a) Prices are per the following units: Albumin per 10g; IVIg per gram; other products are standard units. IVIg(D) represents domestically produced IVIg; IVIg(M) represents the pooled average of the two brands of imported IVIg products

Policy Decisions and Policy Initiatives

Governments can take decisions, which affect supply side costs. The example of leucodepletion was given above in the case of upward pressure on supply costs.

At the same time, policy initiatives can act to reduce supply side cost pressures. The introduction of the OBFM is an example. The eventual introduction of payment for product on the basis of verified receipt will be a policy decision, which acts to contain supply side pressures.

$0.00

$200.00

$400.00

$600.00

$800.00

$1,000.00

$1,200.00

Platelets

Red Cells

FFP

Fractionation

Albumin

PTX

IVIg (D)

IVIg (M)

rFVIIa

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DEMAND SIDE COST DRIVERS

The factors driving demand for blood and blood products in Australia were discussed in the section on Blood Use above. These demand drivers put upward pressure on explicit costs to the blood budget. In as much as they put upward pressure on blood and blood product usage, the factors will also influence the transfusion on costs, and indeed, the full economic costs rise commensurately.

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Best Practice Use

INTRODUCTION

This section considers appropriate use of blood and compares appropriate use (or best practice use) of blood and blood products with the actual use of those products. It defines what is meant by appropriate use and assesses use in Australia against that definition.

The report Options to Manage Appropriate Use of Blood and Blood Products (Sapere Research Group 2011 unpublished) highlights achievements that have been made nationally and among the states and territories in terms of promoting appropriate use of blood and blood products in Australia. The analysis in this section of this report, however, concentrates on identifying where current use might fall below appropriate levels. While the Options to Manage Appropriate Use of Blood and Blood Products report acknowledges that there has been significant progress made towards appropriate use in some areas in Australia, the evidence presented below shows that inappropriate use remains an issue in the sector.

Because the balance of evidence lies in the area of the use of red cells, the discussion of appropriate use below devotes most attention to that product. However, the evidence where available of appropriate use of the other major blood products is also presented.

What Is ‘Appropriate Use’?

BACKGROUND

The WHO Handbook on the Clinical Use of Blood 2001 (Emmanuel, 2001) defines the appropriate use of blood as ‘the transfusion of safe blood products only to treat a condition leading to significant morbidity or mortality that cannot be prevented or managed effectively by other means’

Since the publication of the WHO Handbook, appropriate use has become strongly associated with use of blood and blood products in accordance with published guidelines.

Australia followed the release of the Handbook with the promulgation of the NHMRC / Australian Society of Blood Transfusion Inc. (ASBT) Clinical Practice Guidelines on the Use of Blood and Blood Components in 2001 (National Health and Medical Research Council, 2001b). Since then, Australia has been a leader in developing guidelines to support more appropriate use of blood and blood products.

The NHMRC/ASBT Blood Components guidelines, which cover the use of red cells, are the main guidelines used in Australia. The IVIg Criteria are currently under review. The promulgation of the NHMRC/ASBT Blood Components guidelines (National Health and Medical Research Council, 2001b) prompted others, including the professional Colleges and Societies, to publish complementary guidelines and tools for use by their members to achieve increased appropriate use of blood products.

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FIGURE 74: PRESCRIBING BLOOD COMPONENTS: CHECKLIST FOR CLINICIANS

Source: ASBT Clinical Practice Guidelines – Appropriate Use of Red Blood Cells – October 2001 (National Health and Medical Research Council, 2001a)

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The WHO Clinical Use of Blood guidelines, although promulgated a year earlier than the Australian guidelines, have a more holistic and positive approach to specifying appropriate use by focussing more on patient outcomes through a patient‐centred approach than on the use of fresh blood products. At the same time, they highlight the lack of evidence for transfusion and the risks of transfusion. The NHMRC/ASBT Blood Components guidelines have a strong products focus, concentrating more on the characteristics of inappropriate use, the lack of evidence for transfusion and the risks of transfusion.

In the Australian Council of Healthcare Standards Evaluation and Quality Improvement Program (EQuIP), the third clinical standard (in EQuIP 4 Standards and Criteria of the Australian Council of Healthcare Standards) is the appropriateness of care29. Here ‘appropriateness’ means to provide the ‘right treatment in the right way so that the desired outcome is achieved’.

Clearly the guideline documents have provided sound guidance to clinicians about appropriate use and the risks of transfusion. The EQuIP 4 Standard provides a more recent, patient‐centred definition of appropriateness of care in transfusion practice.

DEFINITION OF ‘APPROPRIATE USE’

In light of the above, this report interprets appropriate use to be adherence to the WHO definition of appropriate use above. This is to be measured by:

compliance with published clinical guidelines;

safety and quality of patient outcomes.

The WHO Handbook on the Clinical Use of Blood takes a cautious approach in relation to blood transfusions. The Handbook says that blood transfusion can be a life‐saving intervention. However, like all treatments, it may result in acute or delayed complications and carries the risk of transfusion‐transmissible infections. The safety and effectiveness of transfusion depend on two key factors:

a supply of blood and blood products that are safe, accessible at reasonable cost and adequate to meet national needs; and

the appropriate clinical use of blood and blood products.

Further, transfusion is often unnecessary for the following reasons:

the need for transfusion can often be avoided or minimized by the prevention or early diagnosis and treatment of anaemia and conditions that cause anaemia;

transfusions of whole blood, red cells or plasma are often given when other treatments, such as the infusion of normal saline or other intravenous replacement fluids would be safer, less expensive and equally effective for the treatment of acute blood loss;

patients’ transfusion requirements can often be minimized by good anaesthetic and surgical management;

29 More information on EQuIP 4 can be found at www.achs.org.au/EQuIP4review.

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if blood is given when it is not needed, the patient receives no benefit and is exposed to unnecessary risk;

blood is an expensive, scarce resource. Unnecessary transfusions may cause a shortage of blood products for patients in real need.

IS USE ‘APPROPRIATE’ IN AUSTRALIA?

INTRODUCTION

There is a substantial degree of evidence in the literature indicating that many transfusion practices in Australia are inappropriate in terms of non‐compliance with clinical guidelines, in terms of the risks that they pose to patients or because they are unnecessary for the patient’s wellbeing. Most of the studies referenced in this section of the report relates to the transfusion of red cells, as the greatest bank of evidence exists in this area. The section, however, also provides an assessment of evidence regarding appropriate use of other blood products where evidence was available.

The authors acknowledge that much of the evidence presented in this report which concerns risks associated with the transfusion of red cells, is drawn from observational studies, rather than RCTs. There is some controversy within the sector as to the acceptability of the evidence. In this regard, the authors highlight a recently released paper by Isbister, J.P., et al. (2011) in Transfusion Medicine Reviews, where the authors remark:

the transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, ‘the blood supply is safer than ever,’ data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognised serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes … comes from observational studies, and a broad and critical analysis to evaluate causation is overdue.

Isbister, J.P., et al. go on to point out that because of the already recognised serious hazards of allogeneic transfusion, the Precautionary Principle and ongoing evidence of inappropriate blood transfusion, causation, not the demand for RCTs should be what drives clinicians and researchers, including those that develop clinical practice guidelines for transfusion. Moreover, the challenge of establishing causation between transfusion and adverse outcomes, in the absence of or while awaiting evidence from large well‐designed and conducted RCTs, is a central theme of their review. The article contains more justification for the applicability of observational studies for guiding review of current transfusion practice. More details of this study are provided at Appendix 5.

The next section makes an assessment of the appropriateness of use of blood and blood products in Australia, against the definition outlined above. That is, evidence is considered regarding:

adherence to relevant clinical guidelines;

the safety and quality of patient care as a result of transfusion practice.

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DOES TRANSFUSION PRACTICE ADHERE TO CURRENT CLINICAL GUIDELINES?

Studies from both Australia and overseas indicate there is a significant gap between what is known from the best available research and what actually happens in clinical practice, including in transfusion practice. This section of the report looks at the evidence in relation to adherence in Australia and overseas to the various guidelines for clinical practice, particularly for the use of blood and blood products.

In Australia, the coverage of clinical guidelines is not comprehensive across all blood products. The relevant clinical guidelines for the administration of blood components are the NHMRC/ASBT Blood Components guidelines. Use of IVIg is governed by the IVIg Criteria issued in December 2007. There are no specific national clinical guidelines for the general use of Prothrombinex‐VF. However, there are the Consensus guidelines for warfarin therapy which were issued in 2000 (Gallus, 2000) followed by a Position Statement: warfarin reversal: consensus guidelines, on behalf of the ASTH in 2004 (Baker, 2004). The Approved Product Information – Prothrombinex also provides some guidance on use of the product (CSL Group, 2010). Albumin use is not subject to any clearly identifiable guidelines. However a number of recent studies have concerned its use in particular circumstances, as will be discussed below.

In general, the following discussion shows that there is evidence that a significant amount of red cell use in Australia contravenes the current guidelines, especially in relation to its use for iron deficiency anaemia. In terms of a measure against current guidelines, the level of IVIg used inappropriately is very small. No other evidence exists concerning the appropriateness of use of the other blood products in focus in this report.

The reasons why adherence to clinical guidelines can falter are discussed later in this section.

Red Cells

The NHMRC/ASBT Blood Components guidelines refer to studies estimating that between 16‐50 per cent of red cell transfusions in Australia may be inappropriate (National Health and Medical Research Council, 2001b). It should be noted that these guidelines are being extensively reviewed and redeveloped (see ‘Other Factors Affecting Supply and Demand’ under Future Trends below. A 2005 report referred to ‘a failure of contemporary Australian transfusion practices to align with recommended best practice.’ (Boyce, 2005) Other studies continue to show that, despite published guidelines, wide variations in transfusion practice exist between countries, institutions and between individual clinicians within the same institution (Bateman, 2008; Gombotz, 2007; Hutton, 2005; Karkouti, 2007; Rao, 2008; Shehata 2007; Snyder‐Ramos 2008).

Most published guidelines, (Audet, 1992; Nuttall, 2006; Ferraris, 2007; Simon, 1998) including the NHMRC/ASBT Blood Components guidelines now recommend a transfusion trigger of around less than 60 to less than 70 g/L for haemodynamically stable patients. They also note that lower thresholds may be acceptable in some patients who are asymptomatic and/or where other specific therapy is available. Transfusing a patient with a Hb level greater than 70g/L may be appropriate if there is evidence of ischaemia, ongoing blood loss and/or other risk factors, however, the guidelines unanimously maintain that transfusion in patients with Hb levels greater than 100 g/L is not indicated.

The NSW CEC (Clinical Excellence Commission, Undated), through its Blood Watch teams conducted a comprehensive red cell audit within its major facilities. The combined audits included 323 transfusion episodes. Of these, 4 per cent of patients received red blood cell transfusion with Hbs over 100g/L, which is outside the NHMRC/ASBT Blood Components

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guidelines. 95 per cent of patients had post‐operative red cell transfusion with Hb above 70g/L and, of those, 83 per cent received a transfusion without evidence in the medical record of clinical indication for transfusion.

An audit of WA transfusion practice in 2008 (Western Australian Department of Health, 2008) demonstrated that 53 per cent of transfusions in Perth metropolitan hospitals were administered to patients with a baseline Hb greater than 80g/L and 8 per cent to patients with Hb greater than 100g/L. A mean of 2.4 red cell units transfused and a mean post‐transfusion Hb rise of 20 g/L suggest that the majority of transfusions were in non‐bleeding patients. A total of 85 per cent of all transfusions resulted in post‐transfusion Hb levels of more than 90 g/L.

Victoria’s Better Safer Transfusion (BeST) program (Victorian Government Department of Health, 2006a) analysed data from 20 Victorian and Tasmanian hospitals (15 public hospitals and five private hospitals) that performed relatively high numbers of elective orthopaedic surgery in 2005‐06. The audit found blood conservation strategies were currently not commonly applied in elective orthopaedic surgery. Such strategies were relatively more commonly used in the private hospital sector. Intra‐operative salvage of blood or post‐operative salvage of blood was performed in 10 per cent of patients. Use of Cell Salvage was reported by 11 of 20 participating hospitals (six of 15 public hospitals and all five private hospitals). There was a wide variation in the proportion of transfused patients within each procedural category between participating hospitals (transfusion rates reported at between 0 per cent and 100 per cent in each procedure category). Overall, in 79 per cent of transfusion episodes the ‘clinical triggers’ for transfusion were assessed as conforming to best practice guidelines. ‘Over‐transfusion’ was deemed to have occurred in 12 per cent of patients and 10 per cent of transfusion episodes. Most instances of ‘over‐transfusion’ occurred intra‐operatively within a relatively small number of contributing hospitals.

Platelets and Fresh Frozen Plasma

The Victorian Department of Human Services published a clinical audit of platelet use (Victorian Government Department of Health, 2008) in 25 Victorian and Tasmanian hospitals (19 public hospitals and 6 private hospitals) in 2007. Of 594 transfusions, 136 or 23 per cent did not align with the NHMRC/ASBT Blood Components guidelines. There was a large variation in range of alignment from hospital to hospital (33 to 100 per cent alignment). The most common reason for platelet transfusion was prophylaxis for bone marrow failure (54 per cent of aligned platelet transfusions) followed by prophylaxis for surgical or invasive procedures (16 per cent of aligned platelet transfusions). The audit highlighted a lack of adherence to documentation of indications for transfusion and reporting platelet counts. Of the 594 transfusions analysed, only 48 per cent complied with the clinical guidelines in these areas.

The NHMRC / Australian Society of Blood Transfusion Inc. (ASBT) Clinical Practice Guidelines on the Use of Blood and Blood Components published in 2001 (National Health and Medical Research Council, 2001b) included recommendations for the appropriate use of FFP, as follows:

patients with significant coagulopathy because of acquired deficiencies of multiple coagulation factors in whom serious bleeding has occurred or for whom emergency surgery or other procedures are planned;

treatment of TTP; and

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treatment of acquired single factor deficiencies where a product containing the specific factor is ineffective or unavailable.

An audit of FFP usage in Victoria and Tasmania conducted in 2005‐06 (Victorian Government Department of Health, 2006b) showed that 66 per cent of the transfusion episodes were consistent with the proscribed clinical practice guidelines and were therefore considered ‘appropriate’.

Inappropriate FFP usage occurred when there was active bleeding, emergency surgery or preparation for major surgery or invasive procedures. In addition, those procedures in which no coagulation tests were determined were categorised as inappropriate. The dosage was deemed appropriate in 42 per cent of the cases examined, although of the remaining 58 per cent of cases, 23 per cent were classified as undetermined because of the absence of a recorded body weight. Dosage was deemed ‘effective’ in 30 per cent of the cases, but in 35 per cent of the ‘ineffective’ cases ‘the absence of a record of post‐translational clinical or laboratory outcomes resulted in effectiveness being categorised as undetermined’.

In a similar audit conducted in South Australia (Hui, 2005) ‘more than 72 per cent FFP was prescribed in an appropriate manner and the majority were monitored adequately’. In this case ‘reversal of warfarin ... emerged as the major indication to transfuse FFP (34 per cent)’.

The Victorian Department of Human Services published a clinical audit of FFP (Victorian Government Department of Health, 2009) in 25 hospitals (21 public and four private hospitals) in Victoria, Tasmania and the ACT in 2008. The use of FFP consistent with the clinical guidelines changed little from a previous audit in 2005 (66 per cent in 2005 versus 68 per cent in 2008). However some individual hospitals showed considerable variance between the two audits. The majority (79 per cent) of aligned transfusions in the audit sample occurred for patients experiencing abnormal coagulation with active blood loss and/or an invasive procedure or surgery. Non‐aligned FFP transfusions were most commonly prescribed to patients for bleeding and/or haemorrhage as well as for plasma exchange. For aligned transfusion episodes, only 17 per cent were considered dose appropriate, 40 per cent were considered not dose appropriate and 43 per cent were ‘undetermined’ largely due to lack of data.


The IVIg Criteria govern the use by clinicians of IVIg paid for under the national blood budget. They are based on the strength of the evidence supporting the use of IVIg for certain clinical conditions. Within the IVIg Criteria, Section 5 conditions (conditions for which IVIg has an established therapeutic role) generally have a strong evidence base, and represent 83 per cent of product use. Section 6 conditions (conditions for which IVIg has an emerging therapeutic role) have a lesser evidence base, and represent 14 per cent of usage. Section 7 conditions (Conditions for which IVIg use is in exceptional circumstances only) have a poorer evidence base and IVIg is issued under Section 7 only in individual exceptional circumstances to treat mostly rare and debilitating conditions (these conditions represent approximately 2 per cent of product use). Subsidised IVIg is not available for Section 8 conditions. The IVIg Criteria are currently under review, including a literature review and an IVIg cost‐effectiveness review.

The Blood Service TMT, in a ‘gatekeeper’ role, provides a consultancy service and issues IVIg based on clinical need. The TMT approves use of IVIg against the IVIg Criteria .

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In Australia, there has been strong growth in IVIg supply to patients with a range of neurological, immunological and haematological indications (as indicated earlier in this report).

The use of IVIg in Australian jurisdictions varies considerably on a per population basis despite the IVIg Criteria being in place and despite the Blood Service playing a national gatekeeping role in accordance with the IVIg Criteria . Figures for estimated usage rates of IVIg in Australia and in comparable countries overseas in 2010, on a per population basis, were provided earlier in Table 32.

As was also discussed earlier in this report (‘State and Territory Patterns of Blood Use‘), there have also been significant differences in growth rates between jurisdictions over time.

Given the increasing demand for IVIg, the Blood Service has undertaken a project to model and forecast future IVIg demand out to 2020 in order to shed light on the possible implications that an increasing demand for IVIg has on future plasma supply requirements. Based on the analysis conducted, the Blood Service currently estimates that IVIg demand will grow to 11,158 kg by 2019‐20, which will require the supply of 1,430 tonnes of plasma for fractionation. This IVIg forecast takes the ageing of the Australian population into account, but does not incorporate future projections in relation to the possible use of IVIg to treat Alzheimer’s Disease (AD). Such estimates are useful in that they enable considerations around the future sustainability of the supply of IVIg in Australia.

The study by Pendergrast, J. M., et al. in Canada in times of shortages of IVIg seems to indicate that it is actual clinical practice in a country that drives use (with only a small effect from availability of product), with stricter adherence to evidence being the one possible way to get IVIg use to be more appropriate. More details of this study are included in Appendix 5.

Prothrombinex‐VF

As noted above, there are no specific national clinical guidelines for the general use of Prothrombinex‐VF. However, there are the Consensus guidelines for warfarin therapy which were issued in 2000 (Gallus, 2000) followed by a Position Statement: warfarin reversal: consensus guidelines, on behalf of the ASTH in 2004 (Baker, 2004). The Approved Product Information – Prothrombinex also provides some guidance on use of the product (CSL Group, 2010).

The Warfarin Reversal Guidelines (Baker, 2004) were published by the Warfarin Reversal Consensus Group. These guidelines were promoted by CSL and the Blood Service, in association with the Australian Society for Thrombosis and Haemostasis (ASTH). The Warfarin Reversal Consensus Group said that, for most warfarin indications, the target maintenance international normalised ratio (INR) is 2‐3. Risk factors for bleeding complications with warfarin use include age, history of past bleeding and specific co morbid conditions. To reverse the effects of warfarin, vitamin K1 can be given. Immediate reversal is achieved with a PCC and FFP. Vitamin K1 is essential for sustaining the reversal achieved by PCC and FFP. When oral vitamin K1 is used for warfarin reversal, the injectable formulation of vitamin K1 is preferable to tablets because of its flexible dosing; this formulation can be given orally or injected. To temporarily reverse the effect of warfarin when there is a need to continue warfarin therapy, vitamin K1 should be given in a dose that will quickly lower the INR to a safe, but not sub‐therapeutic, range and will not cause resistance once warfarin is reinstated.

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Prothrombinex‐HT (now Prothrombinex‐VF) is the only PCC approved in Australia and New Zealand for warfarin reversal. It contains factors II, IX and X, and low levels of Factor VII. FFP should be added to Prothrombinex‐HT as a source of Factor VII when used for warfarin reversal. Simple dental or dermatological procedures may not require interruption to warfarin therapy. If necessary, warfarin therapy can be withheld 5 days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted safely. Bridging anticoagulation therapy for patients at high risk for thromboembolism should be undertaken in consultation with the relevant experts. The management arrangements for this product under the National Blood Arrangements do not require authorisation on a named‐patient basis. However, it is understood that the practice of the Blood Service is to require specific‐patient information for Prothrombinex‐VF release in some cases. Most large hospitals and large private pathology providers keep stocks of it in standard inventory.

Since January 2005 there have been some concerns raised about some of the use of Prothrombinex‐VF, but it does not appear as though inappropriate use is common or widespread. For example, in connection with the devolution of the blood budget in NSW, the Blood Service said (Australian Red Cross Blood Service, 2010a), ‘Clinicians may be influenced to prescribe less expensive products where more expensive products may be more clinically appropriate, leading to suboptimal patient care and increased risk. Example is: Use of Fresh Frozen Plasma instead of Prothrombinex for warfarin reversal’.

There is no doubt that use of Prothrombinex‐VF has risen since the promulgation of the Consensus Guidelines, but there is no real evidence than any of the clinical use associated with that increase in use is inappropriate.

Recombinant Factor VIIa (rFVIIa)

Clinical guidelines for the appropriate use of rFVIIa could not be identified for this report. The product is indicated (and approved) for the control of bleeding in patients with haemophilia with inhibitors and for patients with rare bleeding disorders (National Blood Authority, 2006). Novo Nordisk, the supplier must only accept an Order from an Approved Recipient (as approved by the NBA under its supply Deed (contract) with Novo Nordisk. Approved Recipients for the Product are any hospital, where the Product is ordered specifically for the approved indications in the Deed and any other hospitals approved by the NBA, as notified by the NBA to Novo Nordisk from time to time.

Under the National Blood Agreement the use of rFVIIa (NovoSeven) (National Blood Authority, 2010) is funded to control bleeding episodes and to prevent excessive bleeding associated with surgery in patients who have:

inhibitors to clotting factors VIII or IX; or

congenital FVII deficiency; or

Glanzmann’s Thrombasthenia, for whom platelet transfusion therapy is unsuitable.

Under the NBA arrangements, rFVIIa is not officially authorised on a named patient basis but does require confirmation of use for appropriate purpose (Ibid.). However, because of the cost of the product, some jurisdictions have authorisation arrangements, which do require this, to allow health departments to keep track of product issued under NBA funding.

In June 2006 the JBC was advised that there had been three cases of rare bleeding disorders requiring rFVIIa since the introduction of the new national blood arrangements. JBC agreed that the current AHMC approved policy on rFVIIa usage be slightly reworded to incorporate

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this very minor use. Members endorsed the following policy statement on the use of rFVIIa (Ibid.):

That rFVIIa paid for under the National Supply Arrangement is able to be used for patients with haemophilia (including Acquired Haemophilia) with inhibitors, and patients with rare bleeding disorders like von Willebrand Disorder (with inhibitors), Glanzmann Thrombasthenia and FVII deficiency. Treatment may be for emergency or major bleeds, including haemorrhaging due to surgical procedures and for prophylaxis with planned surgery.

At that time, the JBC also agreed that the NBA re‐negotiate the Novo Nordisk Deed to include the approved indication for rFVIIa as:

The product is indicated for the control of bleeding in patients with haemophilia with inhibitors and for patients with rare bleeding disorders.

DOES CURRENT TRANSFUSION PRACTICE PROMOTE SAFETY AND QUALITY OF PATIENT CARE?

There is much evidence that calls into question the effect of blood products in terms of the safety and quality of patient outcomes. In general, this evidence relates most strongly to red cells and other blood components. However, there are also recent studies concerning safety and quality in the use of albumin. In this sense, there may be a significant degree of use of these products, which could be called inappropriate.

There was no evidence suggesting that other blood products present unacceptable risks to patient safety and quality of care.

The evidence presented in this section of the report comes from Australia and overseas.

The Evidence Base For Use of Red Cells

Inappropriate and avoidable transfusions of allogeneic blood components continue despite an expanding and compelling literature suggesting that not only is there a lack of evidence for indications and benefit from transfusions, but concern that transfusion may be the cause of harm to patients. This section of the report presents a synopsis of Australian and overseas studies which highlight risks to patients in terms of increased mortality and morbidity from allogeneic blood transfusions. It presents evidence that some of these risks appear to be dose‐dependent and some could also be associated with the age of red cells at the time of transfusion.

In addition to a burgeoning literature highlighting such risks, there exists by comparison very little evidence supporting the efficacy of the use of red cell transfusion, particularly in relation to treatment of iron deficiency anaemia. This fact has most recently been recognised in the NBA PBM Guidelines: Module 2 ‐ Perioperative (Pre‐Public Consultation Draft version) (National Blood Authority 2011c).

The draft NBA PBM Perioperative Guidelines are based soundly on the evidence gathered in a systematic literature review, which was conducted to answer a set of research questions, and the review and analysis of that evidence which is presented in four Technical Reports (National Blood Authority 2011a; 2011b; 2011d; 2011e). The NHMRC definitions of evidence grades were employed to underpin the Recommendations for clinical practice and the Practice Points in the draft NBA PBM Perioperative Guidelines. The NHMRC definitions of

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evidence grades for recommendations (National Health and Medical Research Council, 2009) are as follows:

Grade A – Body of evidence can be trusted to guide practice

Grade B – Body of evidence can be trusted to guide practice in most situations

Grade C – Body of evidence provides some support for recommendation(s) but care should be taken in its application

Grade D – Body of evidence is weak and recommendations must be applied with caution.

These evidence grades for recommendations are in turn based on the conventional levels of evidence used by the NHMRC, that is, Levels I, II, III‐1, III‐2, III‐3 and IV (Ibid.). The evidence in the four NBA Perioperative PBM Technical Reports is then analysed and presented in accordance with the ‘NHMRC Evidence Statement’ approach for guidelines developers (Ibid.). In this approach the key research questions are examined against five headings—evidence base; consistency; clinical impact; ability to be generalised; and applicability—to come up with a critical appraisal of individual studies included in the body of evidence compiled through the systematic literature review. For example, if ‘evidence base’ is the consideration for a particular research question, then the grades for recommendations, which can be derived, are:

Grade A – One or more Level I studies with a low risk of bias or several level II studies with a low risk of bias

Grade B – One or two Level II studies with a low risk of bias or Systematic Review/several Level III studies with a low risk of bias

Grade C – One or two Level III studies with a low risk of bias or Level I or II studies with a moderate risk of bias

Grade D – Level IV studies or Level I to III studies/Systematic Reviews with a high risk of bias.

In the draft NBA PBM Perioperative Guidelines these levels of evidence and grades are then combined into:

evidence‐based recommendations, where the NBA reference group considered there was sufficient evidence30 available from the systematic literature review to support the recommendation; and

‘practice points’, where the NBA reference group considered there was insufficient evidence available from the systematic literature review, but where clinicians required guidance to ensure good clinical practice.

Examples are provided on the following page.

30 The grade of evidence and the relevant section of the guidelines document are cited.

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Recommendations (National Blood Authority 2011c)

No. Grade Recommendation Relevant

section of

document

R1 C Health‐care services should establish a multidisciplinary, multimodal

perioperative PBM program (Grade C). This should include

perioperative optimisation of red cell mass and coagulation status,

meticulous attention to surgical haemostasis and minimisation of

perioperative blood loss.

3.1

R2 B

C

In patients undergoing cardiac surgery, preoperative anaemia should

be identified, evaluated and managed to minimise RBC transfusion

which is associated with an increased risk of morbidity (Grade B),

mortality, ICU LOS and hospital LOS (Grade C).

3.3

Practice Points (National Blood Authority 2011c)

No. Practice Point Relevant

section of

document

PP1 To implement the above recommendations, a multidisciplinary, multimodal

perioperative PBM program is required. All surgical patients should be

evaluated as early as possible to coordinate scheduling of surgery with

optimisation of the patient’s Hb and iron stores.

3.3

PP2 RBC transfusion should not be dictated by a Hb ‘trigger’ alone, but should be

based on an assessment of the patient’s clinical status. In the absence of

acute myocardial or cerebrovascular ischaemia, postoperative transfusion is

inappropriate for patients with a Hb level of >70 g/L.

3.3

These NBA evidence‐based PBM Perioperative guidelines take a step in addressing concerns regarding the lack of evidence for benefit of transfusion of blood components and that the current evidence is an imperfect guide to transfusion decisions. These concerns were raised, for example, in the NHMRC/ASBT Blood Components guidelines (National Health and Medical Research Council, 2001b), by the Society of Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists (Ferraris, 2007) and Morton, J., et al. (2010).

The NBA evidence‐based PBM Perioperative guidelines also introduce a paradigm shift in allogeneic transfusion practice, which has been urged by others in the sector. For example, J.P. Isbister (2007) in 2007, focused squarely on patient benefit, not on when, where and how to use certain blood and blood products.

However, in relation to ‘what’ evidence is collated and ‘how’ that evidence is weighted and rated to support recommendations for clinical practice, the NBA evidence‐based PBM Perioperative guidelines, and, presumably, the other guidelines to follow, use the traditional approach to considering evidence. This is the approach required by the NHMRC. This traditional approach to the consideration of evidence to support transfusion has at its heart the principle that the evidence obtained from RCTs is the highest level of evidence (that is,

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Level I) to support practice. However, RCTs are unlikely to be appropriate or ethical in most transfusion settings. It must be said however, that the ‘practice points’ (where the NBA reference group considered there was insufficient evidence available from the systematic literature review, but where clinicians required guidance to ensure good clinical practice) in the NBA evidence‐based PBM Perioperative guidelines take a pragmatic approach to improving the appropriateness of transfusions where insufficient (traditional) evidence is available.

SAFETY AND QUALITY OF BLOOD COMPONENT TRANSFUSIONS

Although blood transfusion may be life‐saving in the setting of critical bleeding, studies show it is also associated with significant risk (Sihler, 2009; 2010) . The risk of known infectious agents such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) has been reduced to very low levels, but the blood supply remains vulnerable to emerging infectious agents (Blajchman, 2006; Stramer, 2009; Wallis, 2009). Transfusion associated circulatory overload (TACO), TRALI (Gajic, 2007; Marik, 2008a) wrong blood component transfused, acute transfusion reactions and bacterial contamination of blood remain the leading causes of transfusion‐related death and major morbidity in High Human Development Index (HHDI) countries.

Of increasing concern is the growing body of literature suggesting that transfusion per se is a risk factor for increased mortality, ICU admission, ICU and hospital LOS and morbidity including increased incidence of infection, septicaemia, ischaemic events (including stroke, myocardial infarction and renal impairment/failure), thromboembolism, multisystem organ failure, systemic inflammatory response syndrome and acute respiratory distress syndrome (ARDS) (Bateman, 2008; Bernard, 2009; Chaiwat, 2009; Corwin, 2004; Croce, 2005; Dunne, 2002; Engoren, 2008; Kim, 2007; Khorana, 2008; Kneyber, 2007; Koch, 2006a; 2006b; 2008; Leal‐Noval, 2001; Malone, 2003; Marik, 2008b; Murphy, 2007; Rao, 2004; Shander, 2009; Surgenor, 2006; Taylor, 2006; Thomson, 2009; Vamvakas, 2010; Yang, 2005). .

The Senior Vice President, Health Affairs and President, UF Shands Health System, in On the Same Page: ‘Saving blood, saving money, saving lives’, 1 October 2010 (Guzick, 2010) wrote to all his staff about the risks, costs, adverse events and benefits associated with transfusion. The article is compelling in relation to the need to change transfusion practice for the benefit of patients and health institutions. Accordingly, it is reproduced at Appendix 5 in full.

In a recent review Tinmouth et al. (2006) concluded ‘we have witnessed a ‘dramatic paradigm shift’ whereby red blood cell transfusions, once regarded as ‘one of the great advances in modern medicine,’ are now considered harmful in some clinical situations.’ An editorial (Jackson, 2006) on the subject cautioned: ‘Despite the robust evidence questioning its efficacy and safety, defiant liberality of PRBC [packed ] transfusion remains. If, like regimented headmasters or detached nihilists, we fail to objectively consider and reject the negative consequences of maintaining a once‐accepted but clearly antiquated paradigm, we do so to the profound detriment of patients.’

In a clinical update in the Medical Journal of Australia in 2010, Saint‐Ryan SP, et al. (2010) found that transfusion of red cells remains an overused treatment for iron deficiency anaemia (Grey, 2008), and that it is also expensive and potentially hazardous. In physiologically compensated patients, transfusion carries unnecessary risks and fails to replenish deficient iron stores. Adequate doses of oral iron can improve Hb concentrations within a few weeks, and IV iron can provide more rapid and predictable increases when clinically important. Transfusion is associated with adverse outcomes, including fluid

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overload (around 1 per cent of patients), and a range of immunological and infectious hazards. Hence, it should be reserved for immediate, targeted management in patients with severe anaemia compromising end‐organ function (for example, angina pectoris or cardiac failure) or where iron deficiency anaemia is complicated by serious, acute ongoing bleeding. Iron therapy should always follow transfusion to replenish iron stores.

Based on an exhaustive literature search on transfusion outcomes, the Scientific Committee of the 1st International Consensus Conference on Transfusion Outcomes (ICCTO) held in Phoenix, Arizona, 3‐5 April 2009 stated: ‘There is a paucity of evidence for benefit and a burgeoning literature demonstrating a strong association between transfusion and adverse outcomes. Despite all available information and escalating costs of blood transfusion, practice remains essentially unchanged. This would not be accepted or tolerated in any other field of medicine in the context of current safety and quality standards’ (Society for the Advancement of Blood Management, 2009).

In 2007 the Society of Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists joined forces to conduct an exhaustive review and produce clinical practice guidelines for perioperative blood transfusion and blood conservation (Ferraris, 2007). These societies emphasised again the lack of evidence for benefit of transfusion and that the current evidence is an imperfect guide to transfusion decisions. They suggest a postoperative transfusion trigger of a Hb value of less than 70 g/L. They also suggested that a higher Hb trigger may ‘not be unreasonable’ in certain patients with risk factors (for example, patients with critical non‐cardiac end‐organ ischemia). However, they qualify this recommendation stating that there is a need for more evidence to support it. The principle recommendation of this expert group was that clinicians employ all available blood conservation methods in patients at risk of blood transfusion. Two recent reviews by Vincent et al. and Klein et al. highlight the limited evidence for benefit in many clinical settings (Klein, 2007; Vincent, 2007).

The objective of a very large retrospective cohort study in 2004 in the US, Morton, et al. (2010), was to assess frequency and outcomes associated with blood products transfusion. Data from the 2004 Nationwide Inpatient Sample database were used. LOS, PIs, non‐infectious transfusion‐related complications, in‐hospital mortality, and total charges were evaluated for transfused and non‐transfused cohorts. The study found patient discharges in the transfused cohort were significantly more likely to have at least one co morbidity than discharges in the non‐transfused cohort (54.5 per cent compared to 47.1 per cent). Of the estimated 38.66 million discharges in the United States in 2004, 5.8 per cent (2.33 million) were associated with blood products transfusion. Average LOS was 2.5 days longer, odds of death were 1.7 times higher, and odds of infection 1.9 times higher for the transfused cohort. More details of this study are included in Appendix 5.

Despite limitations, the Morton study shows that more than 2 million hospital admissions annually are associated with a blood products transfusion and that patients remain at risk of experiencing adverse clinical outcomes. The observation that transfusion recipients experience negative outcomes independent of age, sex, co morbidities, admission type, or DRG assignment warrants further investigation to better identify the appropriateness of current transfusion triggers and to develop and implement more effective approaches to reduce the non‐emergent use of blood in hospitalized patients.

TRALI and incompatibility reactions were not reported for patients identified as transfusion recipients. This finding also warrants further investigation, given that the Joint Commission and the American Association of Blood Banks have established transfusion‐specific performance improvement standards, blood use reviews, and reporting requirements for

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suspected transfusion‐related adverse events. Finally, given that transfusion‐related adverse clinical and health‐related quality‐of‐life outcomes may persist after hospital discharge, additional prospective observational studies are needed to assess the long‐term health status and quality of life of transfusion recipients. In conclusion, raising provider awareness and recognition of the frequency and potential negative clinical outcomes of blood products transfusion—as an independent predictor or surrogate for blood loss—may yield significant clinical and quality‐of‐life benefits at the individual patient level. Equally important is the need to encourage providers to adopt strategies and techniques that are more effective at controlling inadequate surgical haemostasis and that may reduce the frequency of blood products transfusions. More details of this study are included in Appendix 5.

Understanding of the clinical usage of red cells is limited despite its importance in transfusion practice improvement and planning for blood supply requirements. Previous studies have described red cell use based upon ICD and hospital discharge codes. However, such approaches are open to misclassification. The 2010 study by P. J. Barr, et al. (2010) addressed this limitation by undertaking an epidemiological analysis of red cell use using case note review. Patient, disease and contextual factors were extracted from the medical records of a randomly selected sample of hospital patients in Northern Ireland who received a red cell transfusion during 2005 (n = 1474). Transfused patients received a total of 3804 units (median of two units per transfusion episode). Most transfusions occurred in a medical setting (71 per cent). Patients undergoing treatment for gastrointestinal conditions were responsible for the majority of the demand (29 per cent of transfusion episodes; 34 per cent of red cell units).

The presence of bleeding and abnormal tests of coagulation were associated with receiving larger transfusions (‡ 3 units), while patients undergoing orthopaedic surgery and those with a Hb level over 7 g ⁄ dl had the lowest risk of receiving ‡ 3 units in any one transfusion episode. P. J. Barr, et al. concluded that the majority of red cells are now prescribed in a medical setting. P. J. Barr, et al. concluded that with an ageing population and increasing therapeutic interventions, the demand for blood is likely to increase despite efforts to reduce usage by eliminating inappropriate transfusions through education and behaviour change. The post‐transfusion target (and therefore the number of units to transfuse) for any given clinical situation as well as guidance on a ‘safe’ transfusion threshold should be considered in future guidelines.

A study conducted at a hospital in Brazil, is the first large randomized research effort among heart‐surgery patients testing two blood‐transfusion strategies. The study compared ordering a transfusion when the red‐blood‐cell count fell below 30 per cent against waiting until it was under 24 per cent. It found no significant difference in death and other major events within 30 days of surgery between an aggressive approach to transfusions and a restrictive one. In addition, patients who received a transfusion under either strategy had a 20 per cent higher risk of death or other complication from surgery than those who did not.

In two African randomized control trials (Holzer et al. (1993) and Bojang et al. (1997) ) children with severe malaria anaemia received either malarial treatment and whole blood transfusion or malaria treatment alone. There was no significant difference between the transfused and non‐transfused groups although there were significantly more adverse events in the transfused group compared with the non‐transfused group. More details of these studies are included in Appendix 5.

Apart from these two trials, RCTs in transfusion medicine have not evaluated the safety and efficacy of transfusion compared with no transfusion or with some other modality. They

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have been confined to comparing one transfusion strategy with another (that is a restrictive versus a liberal transfusion threshold with thresholds mostly based on a single Hb value). These studies have almost universally found no evidence for benefit from a liberal transfusion threshold. Many studies favour a restrictive policy with reduced transfusion and, in some cases, improved patient outcomes.

In a retrospective study of 1446 patients undergoing bowel surgery multivariate analysis identified perioperative red blood cell transfusion (transfused intraoperatively and up to 48 hours postoperatively), as independently associated with an increased risk of surgical site infections (SSI) (Walz, 2006). As well as the clinical implications of this study, there are possible financial implications as the authors refer to figures estimating that SSIs constitute 20 per cent of nosocomial infections (NI), which are reported to increase costs by approximately $2,000 to $4,500 per patient and extend hospital LOS by 7 to 10 days.

Taylor et al. (2006) identified transfusion being associated with an adjusted dose‐dependent increased risk of NI, ICU and hospital LOS and mortality in 2085 surgical and medical ICU patients. Transfused patients were six times more likely to develop infection compared with non‐transfused. The authors stated, ‘Transfused patients with a better prognosis had higher mortality rates, suggesting that transfusions may do more harm than good in ICU patients who have a reasonably good chance of survival.’ More details of this study are included in Appendix 5.

Zilberberg et al. (2007) conducted a sub‐group analysis of the CRIT study (Anaemia and blood transfusion in the critically ill – Current clinical practice in the United States). They reported a strong independent relationship between packed red blood cell transfusion and the development of ARDS in the ICU (adjusted odds ratio of 2.80). More details of this study are included in Appendix 5.

The improvement of renal allograft survival by pre‐transplantation transfusions alerted the medical community to the potential detrimental effect of transfusions in patients being treated for cancer. Amato A, and Pescatori M (Amato, 2009), conducted a meta‐analysis which aimed to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This was accomplished by validating the results of a previously published meta‐analysis (Amato 1998); and by updating it to December 2004. Amato and Pescatori concluded that the updated meta‐analysis confirmed the previous findings. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seem necessary. More details of this study are included in Appendix 5.

In a multi‐centre prospective observational study of 8004 consecutive patients undergoing isolated coronary artery bypass graft (CABG) surgery the Northern New England Cardiovascular Disease Study Group (DeFoe, 2001) sought to address the question of whether the morbidity and mortality associated with haemodilution anaemia in CABG surgery with cardiopulmonary bypass is due to the anaemia or the red blood cell transfusions used to treat the anaemia. The authors conclude that haemodilution anaemia during cardiopulmonary bypass is associated with an increased risk of low‐output heart failure; however, management of that anaemia with red blood cell transfusion is independently associated with an increased risk of low‐output heart failure. More details of this study are included in Appendix 5.

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In a prospective international multi‐centre study of 5065 cardiac surgery patients, Kulier et al. (2007) found that overall, preoperative anaemia was associated with postoperative morbidity and mortality. Multiple logistic regression analysis revealed that preoperative anaemia was associated with non‐cardiac but not cardiac adverse events. Cardiac adverse events were associated with a combination of preoperative anaemia and co morbidities. Red blood cell transfusion was independently associated in a dose‐dependent manner with increased risk of cardiac and non‐cardiac adverse events. Multivariate analysis revealed preoperative anaemia and red blood cell transfusion were independent but additive risk factors. Patients with low preoperative Hbs had higher rates of postoperative adverse events, but at the same Hb level the risks of adverse events increased with transfusion and the more units transfused the greater the incidence of adverse events.

Transfusion rates remain high in cardiac and orthopaedic surgery and differ widely across physician practices in spite of growing knowledge that allogeneic blood transfusion (ABT) is associated with a risk of PI.

In a prospective observational study Shander, A., et al. (2009) compared the timing and incidence of ABT‐associated PIs in 1,489 orthopaedic or cardiac surgery patients at nine hospitals. Of 455 cardiovascular and 1,034 orthopaedic surgery patients, 415 (55.6 per cent of the cardiovascular patients and 15.7 per cent of the orthopaedic patients) were given ABT. The overall rate of PI during hospitalization was 5.8 per cent. The relative risk of PI was 3.6‐fold greater after ABT (50 patients; 12.1 per cent) than in patients not having ABT (36 patients; 3.4 per cent; 95 per cent confidence interval 2.4, 5.4; p‐0.001). PIs appeared both during hospitalization (n‐86) and within four weeks after discharge (n‐81). Shander, A., et al. concluded that patients should be followed for as long as four weeks after discharge to determine the true incidence and risk of ABT‐associated post operative infection.

Transfusion practices in hospitalised patients are being re‐evaluated, in part due to studies indicating adverse effects in patients receiving large quantities of stored blood. Concomitant with this re‐examination have been reports showing variability in the use of specific blood components. Rogers, Mary A.M., et al. (2009) assessed hospital variation in blood use and outcomes in cardiac surgery patients. They concluded that allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system‐wide immune response. Hospital variation in transfusion practices after CABG was considerable indicating that quality efforts may be able to influence practice and improve outcomes. More details of this study are included in Appendix 5.

Wu et al. (2001) assessed the benefit of transfusion in anaemic elderly patients with myocardial infarction by analysing a United States Medicare/Medicaid database of 234,769 patients. Univariate analysis demonstrated that transfusion was associated with decreased 30‐day mortality in patients admitted with a Hb value less than or equal to 100 g/L, and a trend toward improved survival up to a Hb value of 110 g/L. However, patients transfused with a Hb value greater than 110 g/L had an increased mortality. No multivariate or propensity score matching was performed and the less than 100 g/dL group had twice the number of do‐not‐resuscitate (DNR) orders, more diabetes and fewer aggressive cardiology and cardiac surgery interventions compared with the higher Hb groups, resulting in considerable debate over the relevance of the findings of this study. More details of this study are included in Appendix 5.

A study subsequent to Wu (see above) of patients with myocardial infarction came to a different conclusion. Rao et al. (2004) analysed data from three large international RCT involving 24,111 patients with acute coronary syndrome. After multivariate and propensity analysis, adjusting for timing of events, bleeding, type of infarction, nadir Hb and procedure,

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blood transfusion was associated with a 3.94 times increased risk for 30‐day mortality. When examined by Hb levels, the investigators found an association between transfusion and increased 30‐day mortality at a mean Hb >greater than 83 g/L. The adjusted increased hazard (odds ratio) for death was 168.64 for a mean Hb level of 100 g/L and 291.64 for mean nadir Hb of 117 g/L. They found no association between transfusion and increased mortality and, conversely, no benefit in patients with a mean Hb less than 83 g/L. More details of this study are included in Appendix 5.

Others have sought to evaluate the effects of anaemia and transfusion on tissue or organ hypoxia by looking at their effects on renal function. Swaminathan and colleagues from Duke University examined renal failure in relationship to the lowest haematocrit (Hct) level on bypass (Swaminathan, 2003). They found a direct correlation between the lowest Hct level and postoperative rise in serum creatinine value after heart surgery. However, transfusion did not mitigate this adverse outcome, rather transfusion worsened renal function. Habib and colleagues (Habib, 2005) similarly found that in 1700 patients undergoing coronary artery bypass surgery low Hct level was an accurate predictor of which patients would experience adverse renal function. However the use of transfusion made it worse.

A study, led by Elliott Bennett‐Guerrero (2010), a researcher at Duke University's Duke Clinical Research Institute, found wide variation in transfusion practices at 798 U.S. hospitals, involving 100,000 people receiving coronary‐artery bypass surgery in 2008. Some hospitals gave transfusions to fewer than 10 per cent of their patients, while at others transfusion rates topped 90 per cent. Researchers found that only about 20 per cent of the variation was explained by how sick the patients were. They also found no link between a hospital's use of transfusions and death rates.

A recent editorial in Critical Care Medicine referred to ‘the burgeoning literature relentlessly establishing the deleterious effects of blood transfusion in the critically ill.’ (Jackson, 2005) Numerous studies have demonstrated a strong association between allogeneic transfusion and adverse outcomes including increased short‐ mid‐ and long‐term mortality, morbidity, ICU admission and ICU and hospital LOS (Croce, 2005; Dunne, 2004; Engoren, 2002; Kneyber, 2007; Koch, 2006a; 2006c; 2006d; Kuduvalli, 2005; Malone, 2003; Rogers, 2006; Taylor, 2006; Yamada, 2005).

These studies are retrospective and prospective observational studies and thus, individually, need to be interpreted with caution as there may be unknown confounders not identified by the statistical analysis. However, in recent times the value of large observational studies has been acknowledged as an important tool in identifying safety issues.

Vincent et al. (2002) in an international epidemiologic prospective observational trial of 3534 patients from 146 European ICUs found that the risk of death was increased 33 per cent in transfused patients compared with propensity score matched patients not transfused (28‐day mortality 22.7 per cent compared with 17.1 per cent; P less than 0.02). Transfused had higher ICU mortality (18.5 per cent compared with 10.1 per cent; P less than 0.001) and overall mortality (29.0 compared with 14.9 per cent; P less than 0.001) compared with non‐transfused patients. The investigators also found that transfused patients had an increased length of ICU stay (7.2 days compared with 2.6 days) and a significant increase in diminished organ function.

Malone et al. (2003) in a trauma registry database study prospectively collected data on 15,534 patients admitted to a Level I Trauma Centre over a three‐year period. Patients were stratified by age, gender, race, Glasgow Coma Scale (GCS) score, and Injury Severity Score

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(ISS). After controlling for confounding variables (ISS, GCS score, age, race) and all shock variables (lactate, base deficit, and shock index) blood transfusion was a strong independent predictor of mortality, ICU admission, ICU LOS and hospital LOS. Transfused patients were almost three times more likely to die and greater than three times more likely to be admitted to the ICU. Linear regression analysis demonstrated that patients who received blood within the first 24 hours spent greater than four more days in the ICU than non‐transfused and greater than six more hospital days than non‐transfused. The investigators also identified a dose‐response relationship with increased mortality. Of interest, admission anaemia was identified as an independent predictor of ICU admission, ICU LOS, and hospital LOS, but not mortality.

In an effort to minimise the confounding contribution of injury and shock to outcome, Croce et al. (2005) evaluated the association between delayed transfusion and serious respiratory complications in a cohort of ICU patients with less severe blunt trauma who received no transfusion within the initial 48 hours after admission. They found blood transfusion was still an independent predictor of serious adverse outcome. The authors concluded, ‘This study demonstrates that transfusions are not innocuous and that aggressive pursuit of transfusion substitutes is warranted.’ More details of this study are included in Appendix 5.

Dunne et al. (2004) in a study of 9539 trauma patients found that blood transfusion within the first 24 hours was an independent predictor of systemic inflammatory response syndrome (SIRS) as well as mortality, ICU admission, and ICU LOS. Patients who received blood transfusion in the first 24 hours after trauma had a significantly increased risk of SIRS compared to those not transfused. More details of this study are included in Appendix 5.

Engoren et al. (2002) in a prospective observational cohort study of 1915 patients undergoing CABG surgery used multivariate analysis and propensity score matching to compare transfused versus non‐transfused patients. Patients were followed up for five years. Transfusion was associated with a significantly increased early and late (5‐year) mortality. After adjusting for co morbidities and other factors, transfusion was associated with a 70 per cent increase in mortality.

Two large observational cohort studies (11,963 and 10,289 patients) conducted by the Cleveland Clinic Foundation found that, after adjustment for multiple risk factors, perioperative red blood cell transfusion was associated with a significantly increased early and late hazard for death (p less than 0.0001) in patients undergoing isolated CABG surgery (Koch, 2006a; 2006d). The first study, looking at in‐hospital morbidity and mortality, found that after adjusting for variables known to contribute to a sicker patient profile there was a dose‐dependent relationship between each red blood cell unit transfused and postoperative mortality. Receiving just one unit of red cells had a 77 per cent increased adjusted odds for postoperative mortality, which escalated rapidly after 5 units. Red blood cell transfusion was also associated with a risk‐adjusted increased risk for every postoperative morbid event (renal failure, prolonged ventilatory support, serious PI, cardiac complications and neurologic events).

The second study identified a dose‐dependent relationship between increasing units of red cells transfused peri‐operatively and an incremental decrement in mid‐ to long‐term survival. After controlling for the confounding effects of demographics, co morbidities, operative factors and early hazard for death, survival was significantly reduced (p less than 0.0001) among transfused patients compared with non‐transfused patients up to 6 months (94 per cent v 99 per cent), at 5 years (80 per cent v 90 per cent) and at 10 years (63 per cent v 80 per cent ). Transfusion with as little as one unit was associated with decreased 10‐year survival. The authors concluded, ‘Blood conservation methods should be implemented and

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enforced, and more restrictive transfusion guidelines based on RCT must be put in place to assure a more judicious use of red cells.’

Two subsequent studies by the Cleveland Clinic Group found an association between transfusion and increased risk of postoperative atrial fibrillation and a worse 6 to 12‐month postoperative functional recovery. This study also identified a dose‐dependent relationship, with each unit transfused being associated with incrementally poorer functional recovery. From their data they suggest that a 4‐unit red blood cell transfusion has an equivalent effect on postoperative functional recovery as a PI or neurologic morbid event, and a 2‐unit red blood cell transfusion has an equivalent effect to a preoperative history of chronic obstructive pulmonary disease.

Given the greater postoperative mortality rate in women compared to men following CABG surgery, Rogers and colleagues investigated whether the higher transfusion rate in women may contribute to the gender‐different mortality (Rogers, 2006). They found women were 3.4 times more likely to be transfused than men and received a significantly greater number of units. Women were 1.5 times more likely to die within 100 days of surgery than men. However, when adjusted for blood transfusion, there was no longer a significant difference in the mortality between men and women – suggesting blood transfusion being a risk factor for mortality. The authors conclude that this study suggests the increased mortality in women following CABG surgery is likely due to their increased receipt of blood transfusion. More details of this study are included in Appendix 5.

For some patients, blood transfusion is a necessary and life‐saving intervention; however, many transfusion medicine experts deem blood transfusion an imperfect solution to manage blood loss. Although advances in surgical and anaesthetic techniques have reduced transfusion requirements for some surgical procedures, intraoperative and early postoperative bleeding can be difficult to manage because of anatomy, tissue condition, patient factors, and, at times, surgical technique. Regardless of why it happens, the inability to achieve haemostasis or the inadequacy of rapid surgical haemostasis can contribute to prolonged intensive care time and postoperative morbidity and mortality. Not surprisingly, studies evaluating clinical outcomes among surgical patients have repeatedly reported negative clinical outcomes associated with blood transfusion including higher PI rates, non‐infectious complications such as TRALI, poor postoperative functional recovery, and reduced long‐term survival.

Murphy, G.J., et al. (2007) aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. They concluded that red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs. More details of this study are included in Appendix 5.

Adverse effects of transfusion have also been observed in children. In a study of 295 children admitted to the paediatric ICU (PICU) the mortality rate was 16.4 per cent in the transfused compared with 2.6 per cent in the non‐transfused (P less than 0.001) (Koch, 2006d). Of interest, the investigators found no association between pre‐transfusion Hb levels and mortality. However, they did identify a dose‐dependent relationship between the number of transfusions and increased mortality. Compared with non‐transfused, transfused children had increased duration of ventilatory support (3.2 compared with 11.1 days), vaso‐active agents infused (2.8 compared with 8.2) and PICU stay (3.2 compared with 13.0). After adjusting for confounding factors, the authors found a strong independent association between red blood cell transfusion and increased mortality, ventilatory support, use of vaso‐active agents and PICU stay. Disturbingly, in transfused patients the investigators found an

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‘excess mortality’ among less severely ill children. The authors note that an interesting aspect of their study’s finding is that, in contrast to some other recent studies, this study found these adverse associations despite leucodepleted blood being used. Additionally, a dose‐dependent increase in mortality was observed.

Dr Jacque Lacroix and colleagues (Lacroix, 2007) report on their 2007 international multicenter Transfusion Requirements in the Paediatric Intensive Care Unit (TRIPICU) Study, a trial, described by the authors of the accompanying editorial, as having implications for understanding the role of such transfusions in all critically ill patients. The investigators compared a liberal versus a restrictive transfusion threshold in stable critically ill children. . Results showed that the restrictive transfusion threshold resulted in a 44 per cent reduction in the number of red blood cell transfusions and a 96 per cent reduction in the number of patients exposed to any transfusion when compared with the liberal threshold. This was achieved without any increase in measured adverse outcomes. The authors conclude that a restrictive transfusion threshold in stable critically ill children in ICU can be used safely to reduce transfusion exposure. They caution, however, on applying this finding to other patient groups. After commenting on this trial and reviewing the results of three other randomized trials evaluating transfusion triggers, Drs Howard Corwin and Jeffery Carson in their editorial conclude that the overall evidence does not support liberal use of transfusion in critically ill patients. They state, ‘Red‐cell transfusion should no longer be regarded as ‘may help, will not hurt’ but, rather, should be approached as ‘first do no harm’.’ More details of this study are included in Appendix 5.

Dose‐dependent risks

Data also suggest the existence of a dose‐dependent relationship between units transfused and the risk of experiencing negative outcomes. The inherent risks and adverse outcomes associated with blood transfusion necessitate ongoing efforts to raise awareness of the frequency and clinical impact of blood transfusion in hospitalized patients, to reduce perioperative blood loss and optimize its management, and to minimize the use of blood transfusion. To date, the association of blood transfusion with negative clinical outcomes has primarily been demonstrated in subgroups of surgical patients including CABG surgery, hip and knee replacement, trauma, and colorectal surgery patients.

The NHMRC/ASBT Blood Components guidelines refer to evidence‐based practice guidelines recommending that, when the decision is made to transfuse, ‘blood should be transfused one unit at a time, followed by an assessment of benefit and further need.’ This recommendation is consistent with the recently published Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care (Napolitano, 2009) 13 and data from a large number of recent studies demonstrating that the adverse outcomes associated with transfusion are dose‐dependent, with the risk increasing with each unit given (Banbury, 2006; Basran, 2006; Beattie, 2009; Bernard, 2009; Bochicchio, 2008; Bursi, 2009; Carson, 1999; Chaiwat, 2009; Chang, 2000; Corwin, 2004; Croce, 2005; Dunne, 2002; Gong, 2005; Ho, 2007; Jagoditsch, 2006; Karkouti, 2008; Kneyber, 2007; Koch, 2006a; Koch 2006b; Kulier, 2007; Leal‐Noval, 2001; Malone, 2003; Murphy, 2007; Palmieri, 2006; Rogers, 2006; Rogers, 2007; Salim, 2008; Scott, 2008; Shorr, 2005; Taylor, 2002; Zilberberg, 2007).

The 2004 CRIT study (Corwin, 2004) enrolling 4892 critically ill patients in 284 ICUs similarly found that red blood cell transfusions are independently associated in a dose‐dependent manner (the more blood the patient received, the worse the outcome) with longer ICU and hospital LOS and increased mortality. The number of red blood cell units transfused was significantly associated with increased ICU and hospital LOS compared with patients who did not receive transfusions. Patients with a transfusion amount of 1–2, 3–4, and 4 units had a

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corresponding increase in median ICU LOS of 2.1, 3.8, and 10.1 days, respectively; and an increase in median hospital LOS of 3.5, 6.7, and 16.6 days, respectively, compared with the median ICU LOS of 4.6 days and hospital LOS of 11.0 days observed in the patients who did not receive transfusions.

The objective of a study by Corwin, H.L., et al. (Ibid.) (published in 2004) was to quantify the incidence of anaemia and red cell transfusion practice in critically ill patients and to examine the relationship of anaemia and red cell transfusion to clinical outcomes. It was a prospective, multiple centre, observational cohort study of ICU patients in the United States. Enrolment period was from August 2000 to April 2001. Patients were enrolled within 48 hours of ICU admission. Patient follow‐up was for 30 days, hospital discharge, or death, whichever occurred first. A total of 284 ICUs (medical, surgical, or medical‐surgical) in 213 hospitals participated in the study, and a total of 4,892 patients were enrolled in the study. The main findings were as follows:

the mean Hb level at baseline was 11.0 +/‐ 2.4 g/dL. Haemoglobin level decreased throughout the duration of the study. Overall, 44 per cent of patients received one or more RBC units while in the ICU (mean 4.6 +/‐ 4.9 units). The mean pre‐transfusion Hb was 8.6 +/‐ 1.7 g/dL. The mean time to first ICU transfusion was 2.3 +/‐ 3.7 days;

more RBC transfusions were given in study week 1. However, in subsequent weeks, subjects received one to two RBC units per week while in the ICU;

the number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality;

patients who received transfusions also had more total complications and were more likely to experience a complication;

baseline Hb was related to the number of RBC transfusions, but it was not an independent predictor of LOS or mortality. However, a nadir Hb level of less than 9 g/dL was a predictor of increased mortality and LOS.

Corwin, H.L., et al. concluded that anaemia is common in the critically ill and results in a large number of RBC transfusions. Transfusion practice has changed little during the past decade, and the number of RBC units transfused is an independent predictor of worse clinical outcome.

Zilberberg et al. (2007) also identified an adjusted dose‐response relationship between increasing packed red blood cell units (pRBCs) transfused and increased risk of ARDS. Receiving 1 to 2 units of pRBCs was associated with a greater than twofold increase in ARDS, 3 to 4 units with an almost threefold increase, and greater than 4 units with a greater than fivefold increase, compared with patients not exposed to any pRBC transfusions. More details of this study are included in Appendix 5.

Perioperative red cell transfusion is commonly used to address anaemia, an independent risk factor for morbidity and mortality after cardiac operations. The objective of the 2010 Transfusion Requirements After Cardiac Surgery (TRACS) study by Hajjar, Ludhmila A., et al. (2010) was to define whether a restrictive perioperative red blood cell transfusion strategy was as safe as a liberal strategy in patients undergoing elective cardiac surgery. The study found that, independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days. The authors concluded that, among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in non‐

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inferior rates of the combined outcome of 30‐day all‐cause mortality and severe morbidity. More details of this study are included in Appendix 5.

In a recent article Marik, P.E., and Corwin, H.L (2008a), reviewed and analysed the evidence with the aim of expanding the definition of Acute Lung Injury (ALI) following transfusion. The classic TRALI syndrome is an uncommon condition characterized by the abrupt onset of respiratory failure within hours of the transfusion of a blood product. It is usually caused by antileucocyte antibodies, resolves rapidly, and has a low mortality. A single unit of red cells or blood component product is usually implicated in initiating this syndrome. It has, however, recently been recognized that the transfusion of blood products in critically ill or injured patients increases the risk (OR of 2.13; 95 per cent CI, 1.75–2.52) of the development of the ARDS, 6–72 hours after the transfusion. This ‘Delayed TRALI Syndrome’ is common, occurring in up to 25 per cent of critically ill patients receiving a blood transfusion and is associated with a mortality of up to 40 per cent. Although the delayed TRALI syndrome can develop after the transfusion of a single unit, the risk increases as the number of transfused blood products increase. The management of both the classic and delayed TRALI syndromes is essentially supportive.

A multicentre study of 666 major burn injury patients found an adjusted association between the number of red blood cell units transfused and infection and mortality (Palmieri, 2004; 2006).Heavily transfused patients had a tenfold increase in sepsis, 3‐fold increase in wound infection, fourfold increase in urinary tract infections and a sevenfold increase in ventilator associated pneumonia. There was a 13 per cent increased risk of infection with each unit transfused. Of interest, the authors report that there was wide variation in clinicians’ transfusion thresholds and these actual thresholds varied from their stated thresholds in an earlier survey. The accompanying editorial suggests blood conservation strategies be used to reduce transfusions and calls for further research into methods to reduce blood loss, indications for transfusion and their relationship to patient outcomes (Jeschke, 2006).

Jeschke and colleagues investigated the association between allogeneic blood transfusion and infection and mortality in severely burned paediatric patients (Jeschke, 2007). Even after adjusting for the known effects of increased total body surface area burn and inhalation injury on sepsis, the authors conclude that receiving >20 units of red cells significantly increased the risk of sepsis. Of interest the investigators included weight as a covariate and report that it appears that the total amount of red cells transfused determined the risk, not the relative amount, that is, red cells given per kilogram. More details of this study are included in Appendix 5.

In all of the articles presented above there is a question that must be asked: To what extent did the transfusion practice that caused the infections described vary from guidelines, evidence and the appropriate use of blood products. Some of the articles, Taylor et al. (2006), Rogers, Mary A.M., et al. (2009), Marik, P.E., and Corwin, H.L (2008a), (Palmieri, 2004; 2006) and Jeschke and colleagues (Jeschke, 2007), show transfusion rates remain high to very high in surgery and differ widely across physician practices and between hospitals in spite of growing knowledge that allogeneic blood transfusion (ABT) is associated with a risk of PI which are all clear examples of practice varying from appropriate use.

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Risks associated with the age of red cells

Evidence is emerging that the age of blood at transfusion is probably not neutral or unworthy of consideration as may have been the case to date.

Allogeneic packed red cells suppress immunity and influence outcomes, and the influence of blood on the risk of infection and death may be related to the duration of storage. Hassan et al. (2011) sought to determine whether blood storage duration was associated with infection or death in a large cohort of injury victims. They reviewed a cohort of trauma patients transfused at least 1 Unit of red cells within 24 hours of admission to a level 1 trauma centre.

The outcomes of interest were complicated sepsis and mortality. Hassan, M., et al. compared the amount of older blood (>14 days storage) given to patients who did or did not develop the outcomes of interest using univariate and multivariate methods. A total of 820 patients were included. Patients who died (n = 117) received more units of older blood than those who lived (5 Units [inter quartile range {IQR}, 2‐9] vs. 3 Units [IQR, 2‐6]; P < 0.001). Patients with complicated sepsis (n = 244) received a greater volume of older blood than those without complicated sepsis (6 Units [IQR, 2‐10] vs. 3 Units [IQR, 1‐5]; P < 0.001).

After adjusting for clinical factors, including the total amount of blood transfused, patients receiving greater than or equal to 7 Units of older blood had a higher risk of complicated sepsis than patients receiving 1 or fewer Units (odds ratio, 1.9; P = 0.03). The risk for complicated sepsis and death in trauma victims who are transfused blood is high. The amount of older blood transfused is associated with complicated sepsis. Although the best strategy to minimize the effects of allogeneic blood is to avoid unnecessary transfusions, it may be particularly important to avoid transfusing multiple units of older blood.

A new US study (Koch, 2008) found that cardiac surgery patients who received transfusions of blood that had been stored for 2 weeks or less had lower rates of complications and death than those who received blood that was older. The study was the work of researchers (Koch, Colleen Gorman, Li, Liang, Sessler, Daniel I., Figueroa, Priscilla, Hoeltge, Gerald A., Mihaljevic, Tomislav, Blackstone, and Eugene H) based at the Cleveland Clinic Foundation, Cleveland, Ohio.

In this large observational study, Kock et al. compared 2,872 cardiac surgery patients who received transfusion blood that had been donated within the previous 2 weeks with 3,130 cardiac surgery patients who received transfusion blood that had been donated more than 2 weeks earlier. They found that the patients who were given older blood had a higher risk of dying in hospital than their newer blood counterparts (2.8 versus 1.7 per cent), and they were significantly more likely to need prolonged ventilation support, have kidney failure, sepsis (inflammation affecting the whole body), or multiple organ failure.

The Cleveland Clinic investigators also discovered a direct ‘dose response’ relationship between days of storage and the chances of a combination of serious complications or adverse events. After eliminating potential confounding factors, an analysis revealed that patients who had received older blood had a significantly higher rate of combined serious adverse events than those who received newer blood. Also, they found that patients who received newer blood had a higher chance of surviving the first year after surgery than those who received older blood (92.6 versus 89.0 per cent).

Editor in chief of Journal Watch (published by NEJM), Dr Harlan M. Krumholz, said that the study raised important questions about usage of old blood in cardiac surgery transfusions. The study findings are likely to be true throughout the US, said Krumholz, adding that: ‘with

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a blood supply in constant demand, finding a solution to this problem will not be easy. For now, it seems reasonable to try to ensure that patients needing transfusions who are at the highest risk for adverse events receive blood that is as fresh as possible.’

Marik et al. (1993) conducted a prospective, controlled, interventional study in 1993 to determine the effect of red blood cell transfusion on gastrointestinal and whole‐body oxygen uptake in a multidisciplinary ICU of a tertiary care teaching hospital. They concluded that they had failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red cells developed evidence of splanchnic ischemia. They postulated that the poorly deformable transfused red cells cause microcirculatory occlusion in some organs, which may lead to tissue ischemia in some organs. More details of this study are included in Appendix 5.

Stored red cells undergo progressive structural and functional changes over time. Koch, C.D., et al. (2008) tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells are stored for more than two weeks. They concluded that, in patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than two weeks was associated with a significantly increased risk of postoperative complications as well as reduced short‐term and long‐term survival. More details of this study are included in Appendix 5.

Tsai (2010) reviewed the experimental evidence showing systemic and microvascular effects of blood transfusions instituted to support the organism in extreme haemodilution and haemorrhagic shock, focusing on the use of fresh versus stored blood as a variable. The question: ‘What does a blood transfusion remedy?’ was analysed in experimental models addressing systemic and microvascular effects showing that oxygen delivery is not the only function that must be addressed. Tsai concluded that fresh blood is intrinsically a better resuscitation fluid than older, stored blood in the animal model systems in which it has been carefully studied.

Tsai also concluded that it is apparent that blood transfusions are called for to restore oxygen carrying capacity, while one of the major problems is deficient microvascular perfusion and function. Further, that it is in fact questionable whether a blood transfusion is the optimal remedy for re‐establishing tissue perfusion in an organism subjected to haemodilution and haemorrhage, or both. A precise understanding of the mechanisms involved in blood transfusion may be intrinsically impossible, because blood composition per se is a moving target. Distinguishing between ‘fresh’ and ‘old’ red cells overlooks that the distribution of red cell age in the circulation is presumed to be approximately Gaussian, with an average centred at their circulatory half‐life, therefore even ‘fresh’ blood has a fraction of red cells at the end of their cycle.

Tsai also commented that experimental studies in transfusion provide only a preliminary answer to: What is the problem that must be remedied when a blood transfusion is called for? Tsai proposed that oxygen is only one part of the problem, and that microscopic perfusion was the other component, with their relative importance not yet established. However, Tsai remarked that there was evidence that adequate restoration of microvascular perfusion deficiency in anaemia and haemorrhagic resuscitation may be as efficacious as restoring oxygen carrying capacity, therefore potentially significantly reducing the use of blood. More details of the Tsai study are included in Appendix 5.

An abstract entitled Blood Transfusion Increases Hospital Acquired Septicaemia by O'Mara et al., from the Hunter New England Health Service, Australia was presented at the 52nd ASH

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Annual Meeting and Exposition, December 4‐7, 2010, Orlando, Florida (O’Mara, 2010). The abstract said the study showed there was a statistically significant increase in septicaemia following red cell transfusion. The null hypothesis was rejected. The database was examined by the age of red cells transfused and its effect on nosocomial septicaemia. There was a statistically significant effect of older blood on the rate of septicaemia. The study received some publicity in the Australian press in November 2010. A copy of the abstract is at Appendix 5.

‘The functional quality and efficacy of labile blood components has also been questioned (Hogman, 2006). Storage age of transfused blood appears to play a role, because longer storage time of blood (albeit still within the range acceptable by regulators) correlates with higher mortality rates, especially when larger volumes are transfused (Koch, 2008; Weinberg, 2008). The clinical significance, in terms of adverse clinical outcomes, of storage time of blood is thus currently a topic of heated debate and ongoing research, with the issue of ‘aged blood’ being causative for adverse clinical outcome remaining subjudice and a topic of ongoing research and RCTs (Hess, 2010; Tinmouth, 2006). A wealth of supporting in vitro experimental data and animal studies also suggest that storage‐induced changes in labile blood components may render transfused Red cells less efficacious than assumed, and this can further support the link between transfusion and adverse clinical consequences (Cabrales, 2007; Frenzel, 2009; Isbister, 2003; Solheim, 2004).’

QUESTIONS REGARDING THE BENEFITS OF RED CELL TRANSFUSION

A study, led by Elliott Bennett‐Guerrero (2010), a researcher at Duke University's Duke Clinical Research Institute, found wide variation in transfusion practices at 798 U.S. hospitals, involving 100,000 people receiving coronary‐artery bypass surgery in 2008. Some hospitals gave transfusions to fewer than 10 per cent of their patients, while at others transfusion rates topped 90 per cent. Researchers found that only about 20 per cent of the variation was explained by how sick the patients were. They also found there wasn't any link between a hospital's use of transfusions and death rates.

More than half of open‐heart‐surgery patients receive blood transfusions to reduce the risk of complications, but new studies suggest that many of the transfusions provide little benefit (Figure 75)(Winslow; 2010).

Cardiologists warn that unnecessary transfusions incur higher costs, deplete supplies of donated blood and can increase a patient's risk of infection and other serious problems. Several hundred thousand Americans undergo open‐heart surgery each year but there has been little rigorous research to help guide doctors on whether a transfusion is beneficial.

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FIGURE 75: RED STATES ‐ REDUCING THE NUMBER OF BLOOD TRANSFUSIONS DURING SURGERY

Source: Reproduced from WSJ research; Society of Thoracic Surgeons

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Based on a systematic review and analysis of all literature published over 13 years on transfusion and outcomes, the 2009 International Consensus Conference on Transfusion Outcomes (ICCTO) (Simon, 1998), using the RAND/UCLA Appropriateness Method to determine appropriateness of allogeneic RBC transfusion in 450 clinical scenarios of non‐bleeding relatively stable patients found no evidence to support a clinical benefit from transfusion in any scenario where the Hb level was greater or equal to 80 g/L. Based on the available published evidence, the 15‐member international multidisciplinary expert panel concluded that in only 12 per cent of the 450 scenarios was transfusion likely to improve the patient’s health outcome.

SAFETY AND QUALITY OF ALBUMIN USE

The SAFE study, which was published in May 2004 (Finfer, 2004; Safe, 2004) looked at the use of albumin. The SAFE Investigators issued a subsequent report in 2007 (Myburgh, 2007) of a post hoc follow‐up study of patients with TBI who were enrolled in the SAFE study. The study was a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Blood Service, and The George Institute for International Health. The SAFE Investigators concluded that, in patients in the ICU, use of either 4 per cent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. Following the conduct of a post hoc follow‐up study in 2007 of patients with TBI who were enrolled in the study, they concluded that fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline. More details of these studies are included in Appendix 5.

In June 2009, an Access Economics report (Access Economics, 2009) to the Victorian Government stated that routine use of saline to resuscitate individuals with TBI (TBI) as opposed to albumin would significantly reduce mortality associated with brain injury in Australia. The authors noted that their findings were exactly the same as the results of the SAFE Investigators subsequent report in 2007 (Myburgh, 2007). Further, Access Economics noted that the lower mortality rate with the use of saline as compared to albumin would save costs such as productivity losses and burden of diseases due to premature death. They undertook a cost effectiveness analysis based on economic modelling which estimated that the total Disability Adjusted Life‐Years averted was 17,915 with a net benefit of $687.7 million (in net present value terms), and a benefit/cost ratio of 10.52.

It is particularly noteworthy that:

neither the authors of an Editorial in the Medical Journal of Australia in September 2004 (Finfer, 2004) which noted that the recent publication of the SAFE study brings certainty to the issue of albumin’s safety in a heterogeneous population of adult ICU patients, nor any other appropriate individuals, organisations or professional associations in Australia or New Zealand provided commentary or opinion in the public domain, including in peer‐reviewed journals on the significant findings of either the SAFE Investigators subsequent report in 2007 (Myburgh, 2007) or the Access Economics report of 2009 (Access Economics, 2009);

these two reports were published in a period when use of albumin (including 4 per cent albumin) was on the rise in Australia; and

following the publication of the 1998 Cochrane Injuries Group Albumin Reviewers systematic review (Cochrane, 1998) the use of albumin fell dramatically in Australia, and elsewhere, to reach an all‐time low in 2003‐04 (growth in the use of albumin then commenced to rise steadily from 2004‐05 the year following the SAFE Investigators SAFE

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study in May 2004 (Safe, 2004) and the Editorial in the Medical Journal of Australia in September 2004 (Finfer, 2004)).

SAFETY AND QUALITY OF INTRAVENOUS IMMUNOGLOBULIN USE

No direct evidence was found to suggest that IVIg posed unacceptable risks to safety and quality of care. However, the availability of IVIg in Australia relative to clinical need and demand has been reviewed repeatedly since at least the early 1990s. Three approaches have been used to ensure that IVIg is available for the patients who need it most:

aligning the use of IVIg with conditions for which there is evidence of benefit;

increasing the manufacture of IVIg in Australia; and

importing IVIg from overseas suppliers.

Despite much published clinical research on IVIg, evidence for its efficacy and effectiveness in the treatment of many different conditions remains uncertain. This is due to:

the difficulty of conducting rigorous evaluative studies of treatments for rare and complex medical conditions that are often accompanied by equally complex co morbidities;

the difficulty of evaluating outcomes where IVIg is used as a treatment of last resort (as is sometimes the case) after other therapies have failed; and

a lack of monitoring data from all parts of the world on the use and outcomes of IVIg therapy.

Given the variable extent and quality of evidence for IVIg use, successive reviews and guidelines since 1992 have recommended that indications should be categorised according to the quality of the available evidence and whether or not it showed that IVIg was beneficial.

SAFETY AND QUALITY OF RECOMBINANT FACTOR VIIA USE

The AHCDO Guidelines review (2008) reports that recombinant rFVIIa has been widely used in Australia and has proved to be highly effective in the management of bleeding episodes in patients with inhibitors to FVIII or FIX(Australian Health Ministers’ Advisory Council (AHMAC). 2006). Evidence in the literature suggests that it is effective in 79‐92 per cent of such episodes. One study demonstrated that it was effective in over 90 per cent of surgical cases. Apart from the registered and funded use of rFVIIa for the treatment of episodes of active bleeding in haemophilia patients with inhibitors, in Australia and internationally there is a growing use of this agent as prophylaxis‐‐aimed at the primary and secondary prevention of bleeding episodes or the amelioration of those episodes. In these patients the number, frequency and severity of bleeding episodes is monitored on the prophylactic regimen, to determine its efficacy and to guide adjustment of the prophylactic dose size and frequency. Since its release and TGA registration in Australia there has been a steady take‐up of rFVIIa treatment for haemophilia patients with high titre inhibitors.

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Future Trends The aim of this section of the report is to explore future trends in blood and blood product usage, and also the cost implications. A statistical model has been developed to assist in forecasting future impacts.

OUTLOOK FOR MARKET SUSTAINABILITY—DEMAND AND SUPPLY DYNAMICS

In general, the pressures on demand are upward, with the most significant force arising from the ageing of the population. This acts both to raise demand and constrain supply at the same time. In addition, there are other upward pressures on demand and threats to the blood supply.

DEMOGRAPHIC CHANGE—THE AGEING POPULATION

Australia is experiencing an ageing of its population. As was outlined earlier in this report, this will increase demand for most blood and blood products. This is principally because the underlying conditions which blood and blood products are mainly used for also correlate with ageing. The ageing profile of the population is the principle demand driver underpinning the forecast model presented later in this section.

The ageing population also changes the outlook for blood supply. At present, Blood Service collects blood donations from volunteers between the ages of 16 to 70. An ageing population will reduce the pool of potential donors. This affects most, if not all, high human development index (HHDI) countries.

To express the dual effects of dwindling potential supply and growing demand for blood and blood products, Hofmann and Farmer (2009) have recently introduced the metric of TTDR. This ratio relates the population eligible to donate blood to the population deferred from donating due to age restrictions:

PND = population non‐donating

PD= population donating

Based on historic and projected census data the metric indicates for most developed countries, including Australia, that the donor base will be increasingly diminished relative to the non‐donating population (based on existing donations policies). Hence, the TTDR will rise. For Australia, and many countries, Hofmann and Farmer’s work shows that the take‐off year for the TTDR is expected to be 2010 (Figure 76).

TTDR PND

PD

100

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FIGURE 76: TOTAL TRANSFUSION DEPENDENCY RATIO (TTDR), AUSTRALIA

Source: Hofmann A, Farmer S. Unpublished data, compiled from www.census.gov/ipc/www/idb/country.php

TABLE 38: TRANSFUSION DEPENDENCY RATIOS, AUSTRALIA, SELECTED YEARS

1990 2010 2030 2050

PND 0‐14;70+ 4.972.484 6.025.477 8.209.504 9.549.269

PD 11.983.758 15.490.277 17.846.311 19.463.471

TTDR Aust 70+ 41.5% 38.9% 46.0% 49.1%

Source: Hofmann A, Farmer S. Unpublished data, compiled from www.census.gov/ipc/www/idb/country.php

Figure 77 shows the TTDR trend in the states and territories. The effect of differing age profiles can be seen.

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FIGURE 77: PROJECTED TOTAL TRANSFUSION DEPENDENCY RATIOS, AUSTRALIAN STATES AND TERRITORIES, 1990 TO 2040

Source: SRG projections using ABS catalogue 3222.0--Population Projections, Australia, 2006 to 2101, series B.

Information from the Blood Service shows that the bulk of blood donations in Australia in typically are drawn from 40 to 69 year olds (62 per cent in 2009‐10). Data over the period 2004‐05 to 2009‐10 also show that the ratio of total donors to total population has remained between 2.6 and 2.8 per cent. It is not known whether this rate could be increased through greater marketing efforts, or represents capacity on the current policy of voluntary donation.

It is clear that efforts to expand the supply of blood donations in the face of rising blood demand will need to come at a cost, either through greater intensity of marketing; reliance on apheresis collection, as this method requires fewer donors to generate a given level of supply; and/or a change to the voluntary basis of donations policy.

OTHER SIGNIFICANT PRESSURES ON DEMAND

Expanded Clinical Indications—Intravenous immunoglobulin

Demand for IVIg is influenced by ageing, as was discussed earlier in this report. Taking ageing into account, the Blood Service projects IVIg demand to grow by around 276 per cent over the 2010‐11 base year to 2019‐20 (Australian Red Cross Blood Service, 2010b). That equates to an annual average growth rate of around 16 per cent. However, the Blood Service projections show that annual rate of growth accelerating over the period.

The possible approval of IVIg as a therapy for new and emerging indications would put pressure on demand for this product. For example, the results of a current Phase III clinical trial looking at IVIg therapy in AD by Baxter Healthcare Corporation would have a very significant impact on the demand for IVIg if the results show efficacy and if AD is indicated for use in the IVIg Criteria—see also other emerging indications in Table 39.

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TABLE 39: EMERGING CONDITIONS INVESTIGATING IVIG AS TREATMENT

Source: ARCBS Trends and Analysis Report 2009-10

Effective alternative therapies to IVIg are becoming available for some conditions such as specific monoclonal antibodies (for example, rituximab) and thrombopoietin receptor agonists (for example, romiplostin and eltrombopag) for the management of chronic ITP (Australian Red Cross Blood Service, 2009). The availability and widespread use of such alternatives could potentially reduce the future clinical demand for IVIg.

OTHER SIGNIFICANT THREATS TO SUPPLY

Possible Reduction in the Shelf Life of Red Cells

There is increasing research into the relative efficacy of fresher blood. This was discussed in the section on best practice earlier. If there is a reduction in future in the shelf life of red cells as a result of such research, it would place significant pressure on the supply of red cells in the Australian system.

There was very little information on the average age of blood at the time of transfusion. Stakeholders advised that the common practice was to issue blood within the hospital on a first‐in, first‐out basis. This would tend to increase the age of blood at the time of transfusion.

Data from Queensland Pathology, albeit collected over a very short timeframe, showed that only around 25 per cent of red cells were issued for clinical use by the age of 14 days (Figure

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78). These data pertain to all Queensland public hospitals. A significant proportion of red cells (around 18 per cent) were aged over 30 days at the time of transfusion.

FIGURE 78: AGE (IN DAYS) OF RED CELLS AT TIME OF TRANSFUSION, QUEENSLAND PUBLIC HOSPITALS, FEBRUARY‐APRIL 2010

Source: Queensland Pathology unpublished data

The state average age of red cells at time of transfusion is affected by the lower throughput of rural and remote hospitals, which hold onto some blood for longer before redistributing it to higher throughput hospitals. Corresponding figures for the large metropolitan hospital, Royal Brisbane and Women’s Hospital, show that a higher proportion of red cells are issued before at the age of 14 days than for the State overall—around 46 per cent. Nevertheless, this figure falls well short of the Blood Service’s assumed 80 per cent (Figure 79).

FIGURE 79: AGE (IN DAYS) OF RED CELLS AT TRANSFUSION, ROYAL BRISBANE AND WOMENS HOSPITAL, FEBRUARY‐APRIL 2010

Source: Queensland Pathology unpublished data

Safety Threats

In the absence of relevant tests, new and re‐emerging pathogens can lead to short or long term contractions in the available donor pool. A number of new and re‐emerging pathogens which may pose threat to the safety of the blood supply in the future are discussed below.

The occurrence of some of these risks might be exacerbated by patterns of disease arising from climate change. The World Health Organisation (WHO) indicates that diseases such as diarrhoeal diseases, malaria and dengue are highly climate‐sensitive and are expected to worsen as the climate changes (World Health Organization, 2010). For example, studies suggest that climate change could expose an additional 2 billion people to dengue

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transmission by the 2080s. The discussion below highlights dengue and malaria amongst the list of risks to blood supply safety.

WHO notes that climatic conditions strongly affect water‐borne diseases and diseases transmitted through insects, snails or other cold blooded animals. Additionally, changes in climate are likely to lengthen the transmission seasons of important vector‐borne diseases and to alter their geographic range.

WHO identifies people living in coastal regions as among the groups most vulnerable to the health impacts of climate change. This is of note given the high coastal population density, especially on the eastern seaboard.

The following information, which is drawn primarily from the NBA Annual Report, 2009–10, demonstrates that supply safety risks and the development of associated tests or blood supply treatments, are very real and serious concerns that present a challenge to the blood supply.

DENGUE

Dengue remains a disease of concern in all parts of the world. In Australia, the presence of this virus again resulted in the need to restrict blood collections in northern Queensland in the summer of 2009–10.

Tetravalent vaccine is now considered by some researchers to be essential because dengue can be caused by any one of four related virus serotypes of the genus Flavivirus. Research by the La Jolla Institute in the United States supports the hypothesis that subneutralising levels of dengue virus antibodies may exacerbate the disease. Accordingly, the challenge in developing any vaccine is to ensure that recipients develop antibodies to all dengue serotypes.

A number of vaccines are in development or undergoing clinical trials. Sanofi is continuing to test its tetravalent vaccine and hopes to market it in 2015.

CHIKUNGUNYA

Chikungunya is a mosquito‐borne disease that can cause fever, headache, fatigue, nausea, vomiting, muscle pain, rash and joint pain. The disease can be fatal and there is no vaccine. Recently, the US National Institute of Allergy and Infectious Diseases has tested a chikungunya vaccine successfully on monkeys.

As with dengue, the geographic range of chikungunya has increased considerably.

During 2009–10, a significant outbreak of chikungunya affected Thailand, particularly the southern region, including tourist destinations such as Phuket.

In Australia, no cases of local transmission of chikungunya have been reported, although known competent mosquito vectors for chikungunya are to be found here—for example, Aedes aegypti occurs in northern Australia and Aedes albopictus is found on the Cocos, Christmas and Torres Strait islands.

MALARIA

Malaria continues to pose significant health problems for a large part of the world’s population.

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Resistance is developing to one of the main malaria drugs now in use, just as resistance to chloroquine was experienced 50 years ago. Two studies have highlighted the growing problem of resistance to artemisinins in Plasmodium falciparum malaria in Southeast Asia.

However, Australian researchers have discovered how the malaria parasite resists chloroquine. As a result of a belief that an earlier breakthrough implicated a particular gene in this process, biochemist Dr Rowena Martin and her team at the Australian National University have now shown how this gene affects resistance, and this allows the gene to be circumvented when developing new drugs.

Efforts to develop vaccines are continuing, including through the Dutch biotechnology firm Crucell. Crucell has entered into a collaboration with two US‐based organisations—the PATH Malaria Vaccine Initiative and the US Agency for International Development Malaria Vaccine Development Program. The company is already involved in Phase 1 trials of its malaria vaccine with the National Institutes of Health in the US.

WEST NILE VIRUS

West Nile virus has proved a significant problem for the US blood supply. A US study has revealed that the infection rate for West Nile virus in its population is very much higher than was previously thought. It is now known that people infected with West Nile virus may have persistent virus in their kidneys for years, potentially leading to kidney problems. No vaccine currently exists for West Nile virus. There are continuing concerns about the rate of spread of this disease, with newly‐colonised areas appearing in central Switzerland and Italy.

INFLUENZA

The H1N1 2009 influenza virus (swine flu), declared pandemic by the World Health Organization in 2009, has caused serious illness and death.

In Australia, a vaccine for both adults and children became available towards the end of 2009 and was provided free of charge by the Australian Government. Meanwhile, the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) were being used around the world to ameliorate influenza symptoms. Various countries have reported an oseltamivir‐resistant strain of influenza, but this has not yet become a widespread issue.

Around the world, the H1N1 pandemic was seen as a ‘test run’ for the feared pandemic of Avian flu (A(H5N1)). A number of forums have discussed the lessons learned from the world’s response to this pandemic. NBA notes that such forums have provided better understanding of, and planning for, the impact of a pandemic on the blood sector and should further enhance Australia’s ability to manage pandemic events in the future.

One of the concerns about the fast‐spreading H1N1 virus was that there might be a genetic re‐assortment with the more deadly Avian flu virus (H5N1) and that H1N1 might be the vehicle through which H5N1 achieved human‐to‐human transmission. Avian flu is not of immediate concern at the moment in Australia, but it continues to claim lives in a number of countries, including Indonesia, Vietnam and Egypt.

In the ICU of a Melbourne hospital during the H1N1 outbreak last year, it was confirmed that, the sicker patients were, the lower their IgG2 levels were. This observation offered a potential guide to successful treatment. The World Health Organization was alerted at the time, and a paper detailing the research was published in the journal Clinical Infectious Diseases. This development may result in higher demand for immunoglobulin (IVIg) products in the future.

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The NBA monitored the H1N1 pandemic closely for its potential impact on the blood supply in Australia and observed how blood services around the world responded to the outbreak.

OTHER DISEASES

HIV/AIDS

Scientists at the Scripps Research Institute in the US have isolated two antibodies that can prevent patients with HIV from developing acquired immunodeficiency syndrome (AIDS). The discovery is a potential breakthrough in the 20‐year search for an AIDS vaccine and may eventually help to produce a treatment for HIV‐positive patients who develop AIDS.

According to a report in the journal Science, the antibodies are able to neutralise many strains of the HIV virus and they target a more or less stable portion of the virus that researchers had previously overlooked. This target does not experience the mutations that have previously made it difficult to develop an AIDS vaccine.

Companies developing an AIDS vaccine include GeoVax, Bionor Immuno, PhotoImmune Biotechnology, and Mymetics Corporation. A six‐year Phase 3 trial with 16,000 adult volunteers in Thailand has demonstrated that a vaccine combining Sanofi Pasteur’s ALVAC vaccine and AIDSVAX, developed by VaxGen and now owned by the Global Solutions for Infectious Diseases, was ‘safe and modestly effective’ in preventing HIV infection.

Hepatitis B

The number of people in Australia with chronic HBV infection is predicted to increase markedly over the next decade, according to a new report released by the Australian Centre for Economic Research on Health at The Australian National University.

In order to better meet the potential increased risk to the blood supply, the Blood Service will replace its current semi‐automatic nucleic acid testing (NAT) system and duplex assay (for HIV and HCV only) with a fully‐automated system and a new triplex, highly sensitive TIGRIS/Ultrio assay for the simultaneous detection of HIV, HCV and HBV. The new system will enable single donations to be tested for HBV DNA and provide for more efficient process control and greater sensitivity for HBV detection.

Cytomegalovirus

Cytomegalovirus is a common infection in the general community, and antibodies are carried by a significant proportion of the population. It is an important cause of post‐transplant infection. In that setting, where the patients are highly immuno‐compromised, the disease can lead to serious sequaelae. For mothers who suffer primary infection during pregnancy, there is a risk to the foetus. The NBA contracts with CSL Limited to produce cytomegalovirus immunoglobulin and issued just over 50 million international units in 2009–10.

US company Vical is trialling a therapeutic cytomegalovirus vaccine for transplant recipients and developing a prophylactic vaccine for women so that they can be vaccinated against the disease prior to pregnancy. If the trials are successful, there could be significant changes in how these patient groups are treated (noting however, that all vaccines require approval by the TGA before they are used in Australia).

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DONOR SELECTION AND DEFERRAL

Donor selection and deferral is the initial point of screening that maintains the safety of the blood supply. The TGA and the Blood Service regularly review the frameworks around donor selection and deferral, as these must be flexible in order to respond to rapidly emerging threats.

For example, in 2009–10 (following a decision by the Canadian Blood Services, and approved by the TGA in Australia) the Blood Service deferred donations from chronic fatigue syndrome sufferers, as it had been linked in one study to xenotropic murine leukaemia virus related virus infection.

Other issues that impacted on donor selection decision‐making during the year include:

local transmission of dengue virus infection occurring as far south as Townsville;

new guidance for managing human immunodeficiency virus type 1 (HIV‐1) group O infection;

the decision to defer recipients of yellow fever vaccine from blood product donation for two weeks because of the theoretical risk of transmission from a viraemic donor.

Product Safety

NBA notes that debate continues on the nature and timing of testing required to maintain the optimal level of safety for the blood supply, as companies develop an increasing range of testing capabilities and/or specificity. Further, clear criteria will need to be developed against which any further changes to the testing regime measured, especially given the very sound status of, and minimal risks to the blood supply posed by, the system currently in place. Examples of developments in testing and screening technology that emerged during 2009‐10 included:

using the EP–vCJD blood‐screening assay, Amorfix Life Sciences Ltd has tested 19,000 blood donations in France for variant Creutzfeldt‐Jakob disease;

the US Food and Drug Administration has issued guidance for industry on NAT to reduce the possible risk of parvovirus B19 transmission by plasma‐derived products;

the US Food and Drug Administration approved a further use for Roche’s licensed NAT, for screening source plasma in pools comprising up to 96 individual donations;

the Canadian Blood Services will begin testing the blood supply for Chagas disease;

Ortho Clinical Diagnostics announced US Food and Drug Administration approval of a diagnostic assay for the detection of antibodies to HIV types 1 and 2 (Anti‐HIV‐1+2) for use on a single testing platform;

Abbott received approval from the US Food and Drug Administration for its ABBOTT PRISM HIV O Plus test—the first fully automated test to screen blood for HIV‐1 and HIV‐2;

Lateral Grifols Pty Ltd will use a Melbourne facility to build ‘lateral flow’ blood‐typing machines based on a Swiss invention—a hand‐held card that can test blood types in a fraction of the time of older technology. The factory was established with a grant from the Victorian Government and an equity investment from Grifols.

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PATHOGEN INACTIVATION

NBA also reports that progress in the testing and uptake of pathogen inactivation technology has been strong recently. Two main companies are involved—Cerus Corporation and CaridianBCT. Examples of progress include:

Cerus Corporation is developing the INTERCEPT Blood System to inactivate pathogens in red cells for transfusion. The Phase 1 trial of red cells treated with the INTERCEPT Blood System met its primary endpoint, meeting the criteria recommended by the US Food and Drug Administration;

CaridianBCT’s Mirasol Pathogen Reduction Technology received a CE Mark (European approval) for treating platelets suspended in plasma in 2007. It received a CE Mark for FFP and platelets suspended in platelet additive solutions in 2008. The system is currently in routine use in nine countries in Europe, the Middle East and Africa;

CaridianBCT continues to seek further endorsement of its system through research and testing. For example, in March 2010 CaridianBCT announced that a panel of experts had endorsed the effectiveness of the Mirasol Pathogen Reduction Technology System for replacing gamma irradiation—the current standard of care for preventing transfusion‐related graft versus host disease in platelet recipients. The company received a $US5.6 million grant from the US Department of Defence Deployment Related Medical Research Program to allow for the next phase of development for the Mirasol Pathogen Reduction Technology System, designed to improve the safety of whole blood for transfusions in trauma cases.

Aphios Corporation, announced in August 2009 that it had been awarded a Phase 1 Small Business Innovative Research Grant from the National Heart Lung and Blood Institute (NHLBI), US National Institutes of Health, to develop critical fluid inactivation as a generally‐applicable virus and pathogen inactivation technology for human plasma, plasma products and biologics. Aphios argues that current approaches, such as heating or pasteurisation, solvent detergent technique, ultraviolet irradiation, chemical inactivation and filtration, are not always effective against a wide spectrum of human and animal viruses, are sometimes encumbered by process‐specific deficiencies and often result in denaturation of the biologics that they are designed to protect.

PRION FILTRATION

In the United Kingdom, the Advisory Committee on the Safety of Blood, Tissues and Organs—an independent committee that advises the UK Department of Health—recommended the adoption of the P‐Capt prion reduction filter to pre‐treat red cells destined for children born after 1 January 1996. A cost–benefit analysis is now routinely carried out on all new measures to assist the committee in its decision‐making, and it is one of several factors the committee will consider. Implementation of prion filtration was considered not to be cost‐effective under the majority of scenarios modelled for risk. Estimates from the UK National Blood and Transplant Authority say the cost to the National Health Scheme of producing one unit of blood would double—from £50 to around £100 using the filter—so introducing the filter could cost about £100 million.

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NBA notes that, increasingly, governments around the world will need to make difficult choices involving weighing overall risk against the cost of any change.

There are two major companies working in this field:

ProMetic Life Sciences has agreed to collaborate with Abraxis BioScience to develop and commercialise applications of ProMetic’s prion capture technology platform. ProMetic already has arrangements MacoPharma SA for the commercialisation of the P‐Capt prion capture filter and with Octapharma for OctaplasLG, the only commercially‐available prion‐reduced FFP;

Pall Corporation launched a blood filter that simultaneously reduces prions and leukocytes. The Leukotrap Affinity Plus Prion and Leukocyte Reduction Filter System has received a CE Mark.

OTHER TRANSFUSION SAFETY ISSUES

The prevalence of human leukocyte antigen (HLA) antibodies in blood donors, and whether their presence is related to previous transfusion or pregnancy, has been examined. Researchers concluded that HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of whether or not they have had a transfusion, and in female donors without known immunising events. It has been observed that, in women, the prevalence of HLA antibodies continues to increase significantly with the number of pregnancies the woman has had. As a result, the Canadian Blood Services has deferred female plasma donors who have been pregnant even once, because their donations may, by the presence of such antibodies, trigger TRALI in the transfusion recipients.

INCREASING MARKET EFFICIENCY—NATIONAL INTRODUCTION OF BLOODNET

A significant development affecting the efficiency of the blood market is the increasing capabilities for data capture and reporting being pursued by the JBC through the Sector Information Management and Data Strategy. A key element of this is the intended national introduction by NBA of BloodNet. BloodNet will have a number of functionalities that should serve first to increase the efficiency of the response of blood and blood product supply to demand and second to expand the bank of information available for effective demand planning. This should help to reduce supply driven cost pressures.

BloodNet has arisen from the web based ordering and receipting system developed and implemented by the Queensland Blood Management Program (QBMP) in conjunction with stakeholders. This system was known as the Ordering Receipting Blood System (ORBS). The QBMP web site notes that the primary use of ORBS was to facilitate electronic ordering and receipting of blood and blood products in both public and private sectors. It replaced manual fax based or phone based systems for product ordering.

A Proof of Concept trial for the national implementation of ORBS was established by JBC in 2009. The trial was designed to assess the governance arrangements and technical issues that would need to be implemented to ensure that the system could operate at a national level and to define the system’s potential role as part of the wider Sector Information Management and Data Strategy (SIMDS). The report of the evaluation of the trial prepared in December 2010 (National Blood Authority, 2010) indicated that an additional 14 sites drawn from SA, Victoria and Tasmania were added to the original 65 sites across Queensland.

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The evaluation report indicated that the general results of the trial were positive. ORBS was found to offer a sound and robust technical platform that was easily scalable to allow national deployment with strong stakeholder support. It was also found to deliver benefits against the majority of the recommendations in the SIMDS, specifically the independence from suppliers of data systems and in particular, to have the potential to contribute to a range of other JBC priorities, including:

supply chain improvement;

inventory management;

red cell usage data linkage;

sector performance measurement.

The evaluation report indicates that the system has the functionality currently to capture the following information:

AHP data set – data relating to AHP name, codes and location;

supplier data set – data relating to supplier sites, codes, contact details and locations;

inventory data set – data relating to maximum stock levels by AHP, inventory levels by AHP by date and time by component;

order data set – data relating to both stock orders and patient specific orders including actual items and quantities ordered, patient details for patient specific orders and the urgency of the order. It is important to note that ORBS does not capture order amendments which may arise when the Blood Service is unable to supply items ordered as there is no nationally consistent way in which such situations are implemented by the Blood Service in Progesa, although design options are currently underway to support the current negotiations on payment and substitution rules associated with the OBFM;

issue data set – data relating to products and components issued by the Blood Service including item codes, descriptions, modifiers, collection & expiry dates, phenotypes (in short, all of the data on a standard issue note);

receipt data set – data relating to the confirmation of receipt of items issued from the Blood Service by AHPs including feedback on damaged or otherwise incorrect shipments.

These functionalities are very important in terms of enabling supply to respond adequately to demand, and in particular to assess the fulfilment rate of orders by suppliers and to provide comparative data on ordering practice by AHP type.

NBA proposes to enhance the system with several additional functionalities, including, importantly a ‘Fate of Product’ module. It is currently planned that this module include:

transferred data set – record of transfer of components and products from one AHP to another including product characteristics and specific details, reason for transfer and date/time of transfer;

wasted data set—data relating to the wastage of components and products including product characteristics and specific details, AHP item issued to and AHP wasting the item, reason for wastage and date/time of wastage;

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transfused data set—data relating to the transfusion of components and products, patient identifying references, patient demographic details, Registrar, pre and post Hb levels, DRG and date/time of transfusion.

The Fate of Product module appears to have potential in terms of providing the information required in the system for more effective demand planning and monitoring of sector performance. As has been highlighted earlier in this report, there is a severe gap in terms of information on the uses of blood and blood products beyond delivery to the hospital door. The full specifications of the Fate of Product module were not made available to this project. Hence, it is not possible to conclude at this stage whether the identified information gaps in the system will be satisfactorily addressed by the roll out of BloodNet.

It is understood that the JBC will consider endorsing a national roll out of BloodNet by the NBA. It is further understood that the proposal is for the roll out to be on a voluntary basis. Further, it is understood that those AHPs which adopt BloodNet will have the choice of participating in the Wasted and Transfused data sets within the Fate of Product module. NBA advised that most jurisdictions are interested in adopting BloodNet in the public sector and that the private sector has to date also expressed a strong interest in participating in the system although noting that mandating its uptake in the private sector has not yet been tried. However, there remains a risk that the roll out of BloodNet could be patchy and protracted. Critical information in the sector could consequently remain patchy and inconsistent.

Other elements of the Sector Information Management and Data Strategy that are planned for implementation over the next 18 months fall into three major categories, namely

SYSTEM ENHANCEMENT AND EXPANSION

Enhancements to the existing Australian Bleeding Disorders Register (ABDR) to allow direct on line ordering of all clotting factors and consideration of a patient interface

Development and implementation of a laboratory information system interface to allow the capture of all pathology data relating to a blood order requirement

The ordering of all products from all suppliers to be implemented using the ORBS functionality, and therefore provide both total capture of all products ordered and comprehensive fate of product for all products

Provision of remote access for JBC members to the data from all systems that will be made available through the data warehouse (known as ‘Big Red’)

Completion of a gap analysis of the data capture capabilities from vein to vein, which will specifically focus on interfaces with patient administrative systems

Finalisation of the methodology to achieve data linkage across relevant hospital and laboratory information systems on the usage of blood and blood products

Enhancement of supplier KPI reporting

GOVERNANCE

Finalisation of the national performance scorecard for the sector, providing key measures against the agreed nine elements of performance within the health sector for hospitals, suppliers and governments

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Finalisation of a blood sector system data dictionary to ensure consistency in the use of terminology across all systems

Completion of Blood measures – a guide to standardising how to measure blood related activities in hospitals

Enhancing awareness of the strategy, specifically explaining the role of the NBA in national data collection and demonstrating how the strategy will assist AHP’s in complying with the stewardship expectations of AHP’s and their performance against the new blood standards

DATA PUBLISHING AND REPORTING

Publishing of a range of standard reports generated from the systems, specifically:

an annual report from the ABDR including comparisons to like countries and product usage by jurisdiction;

supply plan performance;

ordering and issuage trends.

OTHER FACTORS AFFECTING SUPPLY AND DEMAND

A number of other factors which could have a positive or negative impact on the sustainability of the blood sector are identified briefly below. In general, there was little information available to support any depth of analysis in regard to the magnitude of the impact of these issues.

Changes to clinical guidelines

As indicated earlier in this report, the NHMRC/ASBT Blood Components guidelines is currently under review. Funding and project management is being provided by the NBA on behalf of all governments. The NBA has facilitated the formulation of a Steering Committee, Expert Working Group, and Clinical/Consumer Reference Groups. The review will result in the production of six modules as part of a comprehensive, evidence‐based, PBM Guideline in three phases as follows:

Phase 1: Module 1 ‐ Critical Bleeding/Massive Transfusion and Module 2 ‐ Peri‐operative

Phase 2: Module 3 ‐ Medical and Module 4 ‐ Intensive Care

Phase 3: Module 5 ‐ Obstetric and Module 6 ‐ Paediatric/Neonates.

Each module of the PBM Guideline will be subject to NHMRC approval, (including methodological and peer review) and an independent AGREE II (Brouwers, 2010) assessment.

Clinical demand for IVIg will continue to be strongly influenced by the Criteria for the Clinical Use of Intravenous Immunoglobulin in Australia and its planned revision by mid‐2011.

The availability of IVIg in Australia relative to clinical need and demand has been reviewed repeatedly since at least the early 1990s. Three approaches have been used to ensure that IVIg is available for the patients who need it most:

aligning the use of IVIg with conditions for which there is evidence of benefit;

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increasing the manufacture of IVIg in Australia;

importing IVIg from overseas suppliers.

The impact of the new guidelines on the demand for fresh blood products and IVIg is unquantified.

Treatment Technologies and Techniques

Changes in treatment technologies and techniques can act to increase or decrease demand for blood and blood products. For example, surgical techniques may be developed for previously inoperable conditions. On the other hand, expansion of laparoscopic techniques may reduce the need for transfusion. There was very little information to identify or quantify the outlook in this respect. It was identified that upward pressures on fresh blood use, particularly red cells and platelets, may result from changes in haematology oncology practices which will enable greater throughput of patients, for example:

the expansion of regional haematology oncology day units;

increases in the number of haematologists in some jurisdictions, for example, Queensland;

combined with changes in haematology treatment regimes:

: tending to be more aggressive earlier in the treatment course, resulting in longer survival but patients remaining transfusion dependent for longer periods (National Blood Authority, Undated – a).

Policy Decisions and Policy Initiatives

Some examples of future areas of policy initiative affecting overall demand for blood and blood products could include:

possible devolution by further jurisdictions to devolve blood budgets down from State authority level:

: this decision has already been taken in Queensland, to be implemented from July 2011;

continued or expanded PBM initiatives, which would affect the use of blood components;

further initiatives such as was taken in 2007‐08 with the injection by the Australian Government of up to $600 million over four years from 2007‐08 to the states and territories for the Elective Surgery Waiting List Reduction Plan.

OUTLOOK FOR PRODUCT PRICES

In general, the outlook is for product prices to increase. Market forces dictate that as supply moves to keep pace with rising demand, the supply sector must compete against other sectors of the economy for common resources, such as labour, technology and materials. This leads to a general picture of rising prices.

The trend is exacerbated if supply is constrained in meeting demand, as may well be the outlook for the blood sector. The presence of monopoly, commercial suppliers of certain

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products, particularly the plasma derived products, adds to the risk that prices will rise. This is because there is a lack of competition to help restrain price increases.

There are several other distinct factors likely to act on product prices into the future. These are discussed below.

SAFETY

Information available to the project showed that maintaining the safety of the blood supply against new and re‐emerging pathogens is a highly likely area to raise the prices of fresh blood products.

Safety measures have significantly reduced the risk of transmitting infectious agents such as the HIV, HBV and HCV. International studies show that this has been achieved at high financial cost (Busch, 2005; Jackson, 2003) (Figure 80).

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FIGURE 80: COSTS OF BLOOD SUPPLY SAFETY MEASURES, 1985‐2009, USA

Source: www.flsenate.gov/data/publications/2010/senate/reports/interim_reports/pdf/2010-119hr.pdf

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Testing of the blood supply already represents a significant proportion of total manufacturing cost and would rise with the introduction of new tests.

RISING INTERNATIONAL DEMAND

Australia remains essentially a price taker for overseas sourced products, although purchasing power is enhanced by the monopsony buying power of the NBA.

The force of ageing populations among the HHDI countries will lead to increased demand, likely concomitant with constrained blood supply. This could lead to increases in the prices of internationally sourced products. There was no information available to quantify such an impact.

OUTPUT BASED FUNDING MODEL FOR THE BLOOD SERVICE

The introduction in 2010‐11 of the Output Based Funding Model (OBFM) by NBA, to govern the pricing of Blood Service prices, has moved funding arrangements closer to a market based model. Fresh blood products are now priced according to the model, which ensures that all Blood Service manufacturing, including capital and overhead costs, are reflected in individual product prices. This is done via a cost attribution matrix.

The OBFM has introduced an incentive for the Blood Service to minimise its operational and production costs as it provides for future surpluses from operational efficiencies to be able to be reinvested (up to a limit of $5 million in any year). Reinvestment is subject to ongoing costs being absorbed and is to align with government policy, including:

compliance with regulatory changes;

improvement in the safety and security of the blood supply;

strategies to achieve efficiencies in the Blood Service;

further achievement of national consistencies;

to reduce the product cost;

to provide for a management reserve (risk pool).

It is intended that the first call on surplus funds will be any regulatory or government policy changes and new Business Cases approved by JBC, provided any on‐going costs can be absorbed in existing funding.

The reinvestment facility helps take the pressure of continued calls on budget for funding initiatives with the Blood Service.

Under the model, payment to the Blood Service continues to be made on the basis of products ordered and issued. This historic funding structure presents an incentive for the Blood Service to generate supply irrespective of demand for product. (There was no firm evidence to conclude whether this incentive has led to oversupply in the sector in practice.) However, the OBFM principles state that the optimum goal is change arrangements to payment on receipted delivery against orders. This is contingent upon introduction of an inventory and receipting system, which facilitates this.

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BLOOD FORECAST MODEL

A major element of this project was the construction of a data‐based model capable of forecasting future demand and costs for blood and blood products in Australia. In terms of cost, the model represents the product cost of supply of all blood and blood products listed on the National Supply Plan and Budget for 2010‐11, excluding diagnostic products.

Essentially, the model indicates that the cost of any single blood product is a function of its price and volume. The model is based on projected national prices and jurisdictional volumes for all blood and blood products as supplied by NBA31.

Price has been constructed on the basis of a baseline price, which is then indexed by an assumed price index. In each of the future scenarios provided below, the price indices used for the various products are those advised by the NBA as built into the forward estimates as at end January 2011. For the years beyond 2012‐13 to the end of the forecasting period, the price indices are held at the 2012‐13 levels. Details on the price indices used per product are at Appendix 7.

The volume function is essentially the same as for price. It takes a baseline volume in a given year and inflates it by a volume index. The volume index has been constructed with the capability of incorporating a range of factors affecting demand for blood and blood products into the future, including, for example:

population size and composition (particularly ageing);

changes in clinical practice;

impact of Patient Blood Management strategies;

changes in clinical guidelines, including indicated uses for products;

changes in technology and/or surgical techniques;

changes in patterns of medical conditions associated with transfusion.

A diagrammatic representation of the logic underpinning the model is provided in Figure 81

Very little reliable information was available to be able to construct credible future demand scenarios, at this point in time, other than for population size, and the effects of ageing on red cell consumption. It will be possible to enhance the volume index as greater levels of data come to hand.

This report presents a number of future forecast scenarios, using the model. In summary, these are:

baseline scenario—demographic change;

historical trend scenario—continuation of recent historical growth trajectories;

31 Prices and volumes are taken from the 2010‐11 NBA National Supply Plan and Budget as at 27 January 2011, and prices for 2011‐12 to 2014‐15 as supplied to CTEPC for approval in 2011. These prices are for planning purposes only and may not reflect prices negotiated in individual supplier contracts.

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a series of growth scenarios for IVIg demand and cost, namely:

o low growth in demand;

o medium growth in demand;

o high growth in demand;

o high growth in demand and price.

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FIGURE 81: BLOOD DEMAND MODEL

Source: Sapere Research Group

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BASELINE SCENARIO—DEMOGRAPHIC CHANGE

The baseline scenario projects volumes and costs of blood and blood products taking into account available information on current rates of use and forward projections of population size and ageing. For the purposes of the baseline scenario forecast of demand and costs, the volume index comprises a demographic index. This is product specific.

In the case of red cells, it has been constructed on the basis of information about the relative volumes of use for the three age brackets—less than 40 years old (< 40 years), 41 to 69 years of age and over 70 years old (> 70 years). These relativities were drawn from the Cobain 2007 study (Data on clinical use of red cells, Cobain study, p94). Though a little dated, this was the only published information made available to the project team.

For all other blood products, the baseline scenario assumes a uniform consumption pattern across age groups:

this is because no data was available to inform demographic‐based usage rates.

Under this scenario, prices are indexed according to the values at Appendix 7.

The baseline scenario draws on:

volume and price data provided by the NBA for all blood and blood products, and all Australian jurisdictions;

population projections data obtained from ABS (Australian Bureau of Statistics, 2008).

Baseline Scenario Cost Results

Results are presented below for the future product costs of the national blood supply over the next 25 years. The cost implications are identified at the national level (that is, the cost to all Australian governments), and at the jurisdictional level (that is, the total cost of supply of blood and blood products to each individual jurisdiction).

NATIONAL RESULTS

The product cost of the national blood supply is estimated to be approximately $937 million in 2010‐11. Under the historical trend scenario assumptions, this was forecast to rise to $1.6 billion in 2020‐21, to reach $2.8 billion in 2030‐31, and $3.6 billion in 2035‐36 (the end of the forecast period) (Table 40). This represents an increase in total costs of over 70 per cent over the next ten years. Assuming current contribution rates, the Australian Government share of this expenditure would be 63 per cent, and the combined contribution of the jurisdictions 37 per cent.

Total cost is forecast to grow in real terms, at an average of approximately 3 per cent per annum. Under the assumptions of the model, the real product cost of the blood supply to Australian governments is expected to nearly double in 25 years.

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TABLE 40: BASELINE SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,207 $1,606 $2,124 $2,790 $3,630

Real Costs $ 937 $1,067 $1,255 $1,466 $1,703 $1,958

Source: Results Sapere Research Group Limited model, adjusted for inflation on basis of 2.5 per cent annual inflation as contained in the 2010 Intergenerational Report (Department of the Treasury, 2010)

The main driver of the increase in costs in this scenario comes from the increase in the cost of red cells. To the extent that usage rates of other blood products are positively correlated with age of recipient, this model understates the impact of demographic change on the total blood budget.

Table 41 shows the significant rise in the per capita cost of blood and blood products, including, again, in real terms.

TABLE 41: BASELINE SCENARIO‐‐PROJECTED PRODUCT COST OF BLOOD SUPPLY PER CAPITA

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Cost Per Capita $41.96 $50.36 $65.49 $77.98 $96.93 $120.04

Real Cost Per Capita $41.96 $44.57 $48.98 $53.84 $59.15 $ 64.75

Source: Results of Sapere Research Group Limited model, adjusted for inflation on basis of 2.5 per cent annual inflation as per the Intergenerational Report 2010 (Ibid.)

STATE AND TERRITORY COST RESULTS

The general result is that product cost of the blood supply for those states with relatively younger age profiles will rise more steeply than those with relatively older profiles.The differences between the jurisdictions in the rates of growth rates are very small (Figure 82). However, this is sufficient to create significant divergences in the proportional shares of national blood costs. The relative position of Queensland and Victoria is an example. Their relative shares are on par at the beginning of the period, but significantly diverged by the end of the forecast period.

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FIGURE 82: BASELINE SCENARIO—PROJECTED GROWTH IN PRODUCT COST OF BLOOD SUPPLY, BY STATE AND TERRITORY (NOMINAL TERMS), 2010‐11 TO 2035‐36

Source: Sapere Research Group Limited model

BASELINE SCENARIO PRODUCT VOLUME RESULTS

The results for forecasts of growth in national demand for red cells, platelets and IVIg under the baseline scenario are presented below.

Red cells

FIGURE 83: BASELINE SCENARIO—PROJECTED DEMAND FOR RED CELLS


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The baseline scenario assumptions produce growth in volumes on a per population basis as well (Figure 84 and Table 42). Under the assumptions of the model, the average usage rate for red cells will increase, nationally, from 37 units per 1000 in 2010‐11, to 47 units by 2035‐36.

FIGURE 84: BASELINE SCENARIO—PROJECTED RED CELL DEMAND PER 1000 POPULATION


TABLE 42: BASELINE SCENARIO—PROJECTED RED CELL DEMAND PER 1000 POPULATION, BY STATE AND TERRITORY

CT SW T LD A AS C WA ational

2010‐11 36 35 28 38 43 31 38 33 37

2015‐16 38 37 29 40 45 33 40 34 38

2020‐21 41 39 31 43 47 36 42 36 41

2025‐26 44 41 33 45 50 38 45 39 43

2030‐31 47 43 34 47 53 41 47 40 45

2035‐36 48 45 35 49 55 42 49 42 47


PLATELETS

Figure 85 and Table 43 show the forecast rise in platelet demand under the baseline scenario, by jurisdiction. As indicated earlier, to the extent that platelet demand is

0

10

20

30

40

50

60

Volume per 1000 population (stan

dard units)

ACT

NSW

NT

QLD

SA

TAS

VIC

WA

National

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correlated with an ageing population, these growth trajectories will understate future demand.

FIGURE 85: BASELINE SCENARIO—PROJECTED DEMAND FOR PLATELETS, BY STATE AND TERRITORY


TABLE 43: BASELINE SCENARIO—PROJECTED DEMAND FOR PLATELETS, BY STATE AND TERRITORY

(Volume, standard units)


2010‐11 2,250 35,095 920 40,729 9,155 2,290 33,000 9,100 132,539

2015‐16 2,381 37,055 991 45,106 9,601 2,364 35,303 10,033 142,834

2020‐21 2,509 39,009 1,063 49,516 10,041 2,431 37,604 10,976 153,149

2025‐26 2,631 40,911 1,136 53,904 10,459 2,486 39,858 11,913 163,299

2030‐31 2,744 42,693 1,210 58,200 10,841 2,527 42,004 12,827 173,045

2035‐36 2,848 44,309 1,284 62,346 11,175 2,552 43,998 13,709 182,219


INTRAVENOUS IMMUNOGLOBULIN

Figure 86 and Table 44 show the forecast rise in IVIg demand for the baseline scenario. Information from the Blood Service indicates that IVIg demand correlates positively with

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ageing as well (Other Significant Pressures on Demand, p161). However, as mentioned above, no data were available to the project to measure the impact. The figures below therefore underestimate future IVIg demand, based on current trends.

FIGURE 86: BASELINE SCENARIO—PROJECTED DEMAND FOR INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY


TABLE 44: BASELINE SCENARIO—PROJECTED INTRAVENOUS IMMUNOGLOBULIN DEMAND, BY STATE AND TERRITORY

(Volume, kg)


2010‐11 44 1040 10.9 725 203 87 605 210 2924.9

2015‐16 47 1,098 12 803 213 90 647 232 3,141

2020‐21 49 1,156 13 881 223 92 689 253 3,357

2025‐26 51 1,212 13 960 232 94 731 275 3,569

2030‐31 54 1,265 14 1,036 240 96 770 296 3,772

2035‐36 56 1,313 15 1,110 248 97 807 316 3,961


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HISTORICAL TREND SCENARIO

The scenario presented below was a representation of continued historical growth rates for blood and blood products. This scenario is provided for the purposes of comparison with other growth scenarios only, as the evidence presented in this report indicates that future growth patterns will be different from past growth patterns.

The scenario was based on the 3‐year average national changes in volume for products that:

were in use in both 2008‐09 and 2010‐11; and

which increased or declined by less than 20 per cent per annum over this period.

For any products not fitting this category, the scenario applied the baseline scenario annual growth assumptions.

The price assumptions for the historical trend scenario were the same as for the baseline scenario.

The scenario makes no allowance for population increases, nor for different age‐related usage of red cell products.

Cost Results

The scenario modelling results are given below. The growth in the overall product cost of the blood supply is much higher than under the baseline scenario, both in nominal and real terms.

TABLE 45: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,524 $2,643 $4,712 $8,603 $16,045

Real Costs $ 937 $1,347 $2,065 $3,253 $5,250, $ 8,654 Source: Sapere Research Group Limited model, adjusted for inflation on basis of 2.5 per cent annual inflation as contained in the 2010 Intergenerational Report (Department of the Treasury, 2010)

TABLE 46: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF BLOOD SUPPLY PER CAPITA

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36


Real Cost Per Capita $41.96 $56.21 $80.59 $119.45 $182.39 $286.20

Source: Sapere Research Group Limited model, adjusted for inflation on basis of 2.5 per cent annual inflation as per the Intergenerational Report 2010 (Ibid.)

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FIGURE 87: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY STATE AND TERRITORY

($ million, nominal)


Product Cost Results

The product cost results under the historical trend scenario are summarised in Table 47 for selected blood products.

TABLE 47: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY FOR SELECTED PRODUCTS


Red Cells Albumin IVIg

2010‐11 $291 $23 $164

2015‐16 $450 $35 $296

2020‐21 $737 $54 $625

2025‐26 $1,205 $84 $1,330

2030‐31 $1,971 $131 $2,845

2035‐36 $3,224 $208 $6,104


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FIGURE 88: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF RED CELLS, BY STATE AND TERRITORY



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FIGURE 89: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY FOR IVIG, BY STATE AND TERRITORY



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FIGURE 90: HISTORICAL TREND SCENARIO—PROJECTED PRODUCT COSTS OF SUPPLY FOR ALBUMIN, BY STATE AND TERRITORY



Under the historical trend scenario, red cell demand per 1000 population would rise to 57 standard units in the 10 years to 2020‐21, and to 110 standard units by the end of the forecasting period. By comparison, current red cell use per 1000 population is around 37 standard units.

The corresponding measures of demand for IVIg under this scenario would be 305g per 1000 population in 10 years, and 1407g per 1000 population after 25 years. By comparison, the current use of IVIg per 1000 population is around 121g.

IVIG GROWTH SCENARIOS

No data were available to produce a credible forecast of IVIg demand based on the impact of ageing in the population. However, it is known that on current patterns of use, ageing will cause an increase in demand for the product. As well, there are pressures on expansion of uses for additional clinical indications (Expanded Clinical Indications—Intravenous immunoglobulin, p161) and also possibly on price (Outlook for Product Prices, p173). To gauge the possible range of cost impacts of future IVIg demand and/or price growth, several scenarios have been constructed using the Sapere blood demand model. These are described in more detail below.

Low Growth in IVIg Demand

Under this scenario, IVIg volume was assumed to increase by 2 per cent per annum, for the 10 year period 2014‐15 to 2023‐24. This rate of growth was assumed to be additional to the impact of population growth (accounted for in the baseline scenario). Price movements

0

10

20

30

40

50

60

70Projected Outlays

Millions

ACT NSW NT QLD SA TAS VIC WA

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were unchanged from the baseline scenario. The time period reflects the possible scenario of a step up in demand following, for example, approval for IVIg use for new indications. However, the scenario is constructed essentially for illustrative and comparative purposes.

Under the scenario, the impact on the total product cost of the national blood supply, in nominal terms, is marginal—$1.65 billion by the 10 year period to 2020‐21, compared with $1.61 billion under the baseline scenario. Similarly, per capita costs rise marginally—in real terms, $50.45 by 2020‐21 compared with $48.98 under the baseline scenario.

TABLE 48: LOW IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,219 $1,654 $2,219 $2,933 $3,843

Real Costs $937 1,078 $1,292 $1,532 $1,790 $2,073


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FIGURE 91: LOW IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY STATE AND TERRITORY



TABLE 49: LOW IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF BLOOD SUPPLY PER CAPITA

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36




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The pattern of overall cost growth by jurisdiction, under the scenario, is shown in Figure 92. Queensland would experience the highest growth of 89 per cent over the forecasting period, compared with a national average of 77 per cent.

FIGURE 92: LOW IVIG GROWTH SCENARIO—PROJECTED GROWTH IN PRODUCT COST OF BLOOD SUPPLY, BY STATE AND TERRITORY (NOMINAL TERMS)


The impact on the costs of IVIg itself are summarised in Table 50 and Figure 93. Under the assumptions of the scenario, the total costs of all other products remained the same as for the baseline scenario.

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FIGURE 93: LOW IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



TABLE 50: LOW IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



2010‐11 3 68 1 47 13 6 39 14 190

2015‐16 3 81 1 60 16 7 48 17 233

2020‐21 5 117 1 89 22 9 70 26 339

2025‐26 7 162 2 128 31 13 97 37 476

2030‐31 9 214 2 175 41 16 130 51 638

2035‐36 12 283 3 239 53 21 174 69 854


Medium Growth in IVIg Demand

Under this scenario, IVIg volume was assumed to increase by 5 per cent per annum, for the 10 year period 2014‐15 to 2023‐24. This rate of growth was assumed to be additional to the impact of population growth (accounted for in the baseline scenario). Price movements were unchanged from the baseline scenario. Again, the time period reflects the possible

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scenario of a step up in demand following, for example, approval for IVIg use for new indications. However, the scenario is constructed essentially for illustrative and comparative purposes.

Under the medium IVIg growth scenario, the impact on the product cost of national blood supply, in nominal and real terms, is summarised in Table 51.

TABLE 51: MEDIUM IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,238 $1,740 $2,406 $3,234 $4,336

Real Costs $937 $1,095 $1,359 $1,661 $1,974 $2,340


FIGURE 94: MEDIUM IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY STATE AND TERRITORY



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TABLE 52: MEDIUM IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF BLOOD SUPPLY PER CAPITA COSTS

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36




The pattern of overall cost growth by jurisdiction, under the medium IVIg growth scenario, is shown in Figure 95. Queensland would experience the highest growth of 99 per cent over the forecasting period, compared with a national average of 86 per cent.

FIGURE 95: MEDIUM IVIG GROWTH SCENARIO—PROJECTED GROWTH IN PRODUCT COST OF BLOOD SUPPLY BY STATE AND TERRITORY


The impact on the costs of IVIg itself are summarised in Figure 96 and Table 53. Under the assumptions of the scenario, the total costs of all other products remained the same as for the baseline scenario.

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FIGURE 96: MEDIUM IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



TABLE 53: MEDIUM IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



2010‐11 3 68 1 47 13 6 39 14 190

2015‐16 4 88 1 65 17 7 52 19 252

2020‐21 6 146 1 111 28 12 87 32 424

2025‐26 10 225 2 178 43 18 136 51 663

2030‐31 13 315 3 258 60 24 192 75 939

2035‐36 19 447 4 378 84 33 274 110 1,348


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High Growth in IVIg Demand

Under this scenario, IVIg volume was assumed to increase by 10 per cent per annum, over the years 2014‐15 to 2023‐24. This rate of growth was assumed to be additional to the impact of population growth (accounted for in the baseline scenario). Price movements were unchanged from the baseline scenario.

Under this scenario, the impact on the total product cost of the blood supply, in nominal and real terms, is summarised in Table 54.

TABLE 54: HIGH IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,274 $1,927 $2,882 $4,114 $6,081

Real Costs $937 $1,126 $1, 506 $1, 990 $2,511 $3,280


FIGURE 97: HIGH IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY STATE AND TERRITORY



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TABLE 55: HIGH IVIG GROWTH SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF BLOOD SUPPLY PER CAPITA

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36




The pattern of overall cost growth by jurisdiction, under the high IVIg growth scenario, is shown in Figure 98. Queensland would again experience the highest growth of 122 per cent over the forecasting period, compared with a national average of 106 per cent.

FIGURE 98: HIGH IVIG GROWTH SCENARIO—PROJECTED GROWTH IN PRODUCT COST OF BLOOD SUPPLY BY STATE AND TERRITORY


The impact on the costs of IVIg itself are summarised in Table 56 and Figure 99. Under the assumptions of the scenario, the total product costs of supply for all other products remained the same as for the baseline scenario.

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FIGURE 99: HIGH IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



TABLE 56: HIGH IVIG GROWTH SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



2010‐11 3 68 1 47 13 6 39 14 190

2015‐16 4 101 1 74 20 8 59 21 288

2020‐21 9 211 2 161 41 17 126 47 612

2025‐26 16 387 3 306 74 30 233 89 1,138

2030‐31 26 610 4 499 116 46 371 146 1,819

2035‐36 43 1,024 6 866 193 76 629 254 3,091


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High Growth in IVIg Demand and Price

Under this scenario, IVIg volumes and prices were assumed to increase by 10 per cent per annum, over the years 2014‐15 to 2023‐24. This rate of growth was assumed to be additional to the impact of population growth (accounted for in the baseline scenario).

Under this scenario, the impact on the product cost of the national blood supply, in nominal and real terms, is summarised in Table 57.

TABLE 57: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS

($ million)

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36

Nominal Costs $ 937 $1,314 $2,223 $3,960 $6,950 $13,269

Real Costs $ 937 $1,161 $1,737 $2,734 $4,242 $7,157


FIGURE 100: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF SUPPLY OF BLOOD AND BLOOD PRODUCTS, BY STATE AND TERRITORY



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TABLE 58: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED IMPACT ON PRODUCT COST OF BLOOD SUPPLY PER CAPITA

2010‐11 2015‐16 2020‐21 2025‐26 2030‐31 2035‐36




The pattern of overall cost growth by jurisdiction, under the scenario of high growth in IVIg price and demand, is shown in Figure 101. Queensland would experience the highest growth of 159 per cent over the forecasting period, compared with a national average of 137 per cent.

FIGURE 101: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED GROWTH IN PRODUCT COST OF BLOOD SUPPLY BY STATE AND TERRITORY


The impact on the costs of IVIg itself are summarised in Figure 102 and Table 59. Under the assumptions of the scenario, the total costs of all other products remained the same as for the baseline scenario.

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FIGURE 102: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



TABLE 59: HIGH GROWTH IVIG PRICE/DEMAND SCENARIO—PROJECTED PRODUCT COST OF SUPPLY OF INTRAVENOUS IMMUNOGLOBULIN, BY STATE AND TERRITORY



2010‐11 3 68 1 47 13 6 39 14 190

2015‐16 5 114 1 84 22 9 67 24 327

2020‐21 13 313 3 238 60 25 186 69 908

2025‐26 32 753 6 596 144 59 454 173 2,216

2030‐31 66 1,561 11 1,278 297 118 950 374 4,655

2035‐36 144 3,406 18 2,879 643 251 2,092 846 10,280


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Acronyms and Abbreviations AACB Australasian Association of Clinical Biochemists

AAPP Australian Association of Pathology Practices

ABA American Burn Association

ABD autologous blood donation

ABDR Australian Bleeding Disorders Registry

ABS Australian Bureau of Statistics

ABLE The Age of Blood Evaluation

ABT allogeneic blood transfusion

ACSQHC Australian Commission on Safety and Quality in Health Care

AD Alzheimer’s Disease

AG Australian Government

AGD Attorney‐General’s Department

AGREE Appraisal of Guidelines Research & Evaluation

AHCDO Australian Haemophilia Centre Directors Organisation

AHMAC Australian Health Ministers’ Advisory Council

AHMC Australian Health Minister’s Council

AHP Approved Health Providers

AHS Area Health Services

AIDS Acquired Immunodeficiency Syndrome

AIMS Australian Institute of Medical Scientists

ALI acute lung injury

ALS Australian Laboratory Services

ANH acute normovolaemic haemodilution

ANZICS Australian and New Zealand Intensive Care Society

ANZSBT Australian and New Zealand Society of Blood Transfusion

AO Officer of the Order of Australia

AR Approved Recipient

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ARCBS Australian Red Cross Blood Service

ARDS acute respiratory distress syndrome

ASBT Australasian Society of Blood Transfusion Incorporated

ASC Australian Society of Cytology

ASCEPT Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

ASCIA Australasian Society of Clinical Immunology and Allergy

ASH American Society of Hematology

ASM Australian Society for Microbiology

ASTH Australasian Society of Thrombosis and Haemostasis

AUBRG Appropriate Use of Blood Reference Group

BCA blood conservation algorithm

BCSAC Blood Clinical and Scientific Advisory Committee

BeST Better Safer Transfusion

BMS bloodless medicine and surgery

BTIC Blood Transfusion Improvement Collaborative

CABG coronary artery bypass graft

CARI Caring for Australasians with renal impairment

CCCTG Canadian Critical Care Trials Group

CEC Clinical Excellence Commission

CIDP chronic inflammatory demyelinating polyneuropathy

CIG Cochrane Injuries Group

CRD Centre for Reviews and Dissemination

CRG Clinical Reference Group

CSL CSL Limited

CTEPC Clinical, Technical and Ethical Principal Committee

DHS Victorian Government Department of Human Services

DIC disseminated intravascular coagulation

DNR do‐not‐resuscitate

DOHA Department of Health and Ageing

DPC Department of Premier and Cabinet

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DRG Diagnostic Related Group

EC European Community

EIMS Emergency and Incident Management Services

EQuIP Evaluation and Quality Improvement Program

ESA Endocrine Society of Australia

FEIBA factor eight (VIII) inhibitor bypass agent

FFP fresh frozen plasma

GCS Glasgow Coma Scale

HAC Haemovigilance Advisory Committee

Hb haemoglobin

HBV hepatitis B virus

Hct haematocrit

HCV hepatitis C virus

HDNB Hemorrhagic Disease of the Newborn

HFA Haemophilia Foundation Australia

HGSA Human Genetics Society of Australasia

HHDI High Human Development Index

HISA Health Informatics Society of Australia Limited

HIV human immunodeficiency virus

HSANZ Haematology Society of Australia and New Zealand

HTC Haemophilia Treatment Centres

ICCTO International Consensus Conference on Transfusion Outcomes

ICD International Statistical Classification of Diseases and Related Health Problems

ICU intensive care unit

IDA iron deficiency anaemia

IDFA Immune Deficiency Foundation of Australia

IDMS Integrated Data Management System

IHI Institute of Healthcare Improvement

IIMS Incident Information Management System

INR international normalised ratio

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IREF Ischemia Research and Education Foundation

ISS Injury Severity Score

ITP idiopathic thrombocytopenic purpura

IVIg intravenous immunoglobulin

JACC Japan Collaborative Cohort Study

JBC Jurisdictional Blood Committee

LOS length of stay

MBS Medicare Benefits Scheme

MCA Multi‐Criteria Analysis

McSPI Multicenter Study of Perioperative Ischemia Research Group

MCTG Multicenter Trials Group

MMD multimodality blood conservation group

MOU Memorandum of Understanding

NAT Nucleic Acid Testing

NATA National Association of Testing Authorities

NBA National Blood Authority

NBS National Blood Service

NBTC National Blood Transfusion Committee

NCOPP National Coalition of Public Pathology

NHLBI National Heart, Lung, and Blood Institute

NHMRC National Health and Medical Research Council

NHS National Health Service

NHSBT National Health Service Blood and Transplant

NI nosocomial infection

NICS National Institute of Clinical Studies

NPAAC National Pathology Accreditation Advisory Council

NPBMP National Patient Blood Management Program

NPSL National Product and Services List

NSCCAHS North Sydney Central Coast Area Health Service

NSF National Stroke Foundation

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O&PMs Outcome and Performance Measures

OECD Organisation for Economic Cooperation and Development

ORBS Ordering Receipting Blood System

PAC Pathology Associations Council

PBM Patient Blood Management

PBS Pharmaceutical Benefits Scheme

PBMP Patient Blood Management Program

PCC prothrombin complex concentrate

PI postoperative infection

PICU paediatric intensive care unit

PRBC packed red blood cells

QBMP Queensland Blood Management Program

RACP Royal College of Physicians of Australasia

RAND Research And Development

RBC red blood cell

RCPA Royal College of Pathologists of Australasia

RCT randomised controlled trial

REDS Retrovirus Epidemiology Donor Study

rFVIIa recombinant activated factor VII

rHuEPO recombinant human erythropoietin

SAA Standards Association of Australia

SABM Society for the Advancement of Blood Management

SABSAC South Australian Department of Health’s Blood Sector Advisory Committee

SAFE Saline versus Albumin Fluid Evaluation

SANGUIS Safe and Good Use of Blood in Surgery

SCA The Society of Cardiovascular Anestheiologists

SJOG St John of God

SHOT Serious Hazards of Transfusion

SIRS systematic inflammatory response syndrome

SRG Sapere Research Group

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SSI surgical site infections

STIR Serious Transfusion Incident Reporting

TACO transfusion associated circulatory overload

TBI traumatic brain injury

TCH Canberra Hospital

TGA Therapeutic Goods Administration

THJA total hip joint anthroplasty

TIA transient ischaemic attack

TKA total knee arthroplasty

TMAC Transfusion Medicine Advisory Committee

TMT Transfusion Medicine Team

TNC Transfusion Nurse Consultant

TRACS transfusion requirements after cardiac surgery

TRALI transfusion‐related acute lung injury

TRIPICU Transfusion Requirements in Pediatric Intensive Care Unit

TTDR Total Transfusion Dependency Ratio

TTP Thrombotic Thrombocytopenic Purpura

Tx transfusion

UC usual care

UCLA University of California, Los Angeles

UR Unit Record

VNI Victorian Neurotrauma Initiative

WAPBMP Western Australian Patient Blood Management Program

WHO World Health Organization

A P P E N D I X 1

Terms of Reference

ANALYSIS OF COST DRIVERS AND TRENDS IN THE BLOOD SECTOR

The Consultant shall conduct and report on an analysis of cost drivers and trends in the blood sector, including comparisons with similar countries, and analysis of significant differences in demand between States and Territories. This analysis will be informed primarily by data currently collected by the National Blood Authority, the Australian Red Cross Blood Service and other relevant documentation prepared by States and Territories, to inform the forecast modelling for the National Supply Plan and Budget.

The Consultant will:

Work with a Reference Group comprised of a representative of the Commonwealth, a representative of the Blood Service, and representative/s from the Jurisdictional Blood Committee as specified by the Department;

Undertake consultations with key stakeholders, including but not limited to:

The National Blood Authority;

The Australian Red Cross Blood Service;

Department of Health and Ageing;

Jurisdictional Blood Committee;

National Health and Medical Research Council; and

Other stakeholders as mutually agreed by the Department of Health and Ageing, as required and at the contractor’s discretion.

The Consultant will work with the Reference Group to prepare and deliver to the Department for approval, a draft final report including an executive summary, outcomes and conclusions, which takes into consideration feedback from the Reference Group and any input from the stakeholders outlined above.

The draft final report should consider and explore blood and blood product usage in the blood sector including, but not limited to:

Analysis of comparative rates of international use;

Assessment of data on usage (from the National Blood Authority, the Australian Red Cross Blood Service and other relevant sources) across jurisdictions;

Assessment of the relationship between demand and indications of ‘best practice’, for example, clinical guidelines and criteria nationally and between jurisdictions;

Identification and assessment of other cost drivers for blood and blood products;

Assessment and analysis of the growth and trends of usage of blood and blood products;

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Identification of options for improving the evidence base for the use of blood and blood products including the implementation and uptake of clinical guidelines and criteria.

The report should also:

Identify gaps in currently available data to determine who is using blood, how much they are using, what it is being used for (consistency with best practice guidelines) and how much is ordered but not used;

Consider any additional issues uncovered through the consultation process; and

Estimate future trends of blood and blood product usage.

A P P E ND I X 2

Reference Group Participants

Donna Burton, Assistant Secretary, Blood, Organ and Regulatory Policy Branch, Department of Health and Ageing

Dr Alison Turner, Chief Executive Officer, National Blood Authority

Jennifer Williams, Chief Executive, Australian Red Cross Blood Service

Rachel Allden, Principal Consultant, Blood Organ and Tissues Program, SA Health

Karen Botting, Senior Program Adviser, Blood and Pharmaceutical Programs, Department of Health, Victoria

Geoff Simon, Scientific Advisor, Queensland Blood Management Program, Queensland Health

Dr Gina Clare, Queensland Blood Management Program, Queensland Health

Prof Henry Ekert, Clinical Haematologist, Royal Children’s Hospital, Parkville, Victoria

Dr Chris Hogan, Consultant Haematologist and Transfusion Specialist, Royal Melbourne Hospital (Principal Medical Adviser, National Blood Authority)

A P P E ND I X 3

Data Sources

There were several large datasets used in the analysis for this project. These are detailed in the table below.

Additional specific elements of data were obtained from the literature, and as a result of specific requests, mainly to state health authorities, the Australian Red Cross Blood Service and the Department of Health and Ageing. Relevant sources are noted throughout the text of the report.

DATA SET SOURCE MAIN USE

National Supply Plan and Budget data

2003‐04 to 2009‐10—product prices and

actual volumes

National Blood

Authority

Historical volume and cost

information for blood and

blood products

National Supply Plan and Budget data

2010‐11—planned product prices and

volumes

2011‐12 to 2014‐15—product prices for

planning purposes only

National Blood

Authority

Basis of projections for

future demand and cost

scenarios

National Admitted Patient Care Collection,

2003‐04 to 2008‐09

Department of Health

and Ageing

Hospital separations data,

showing trends in

separations involving

transfusion

Australian Demographic Statistics

ABS catalogue 3101.0

Australian Bureau of

Statistics

Historical per population and

per capita figures

Population Projections, Australia, 2006 to

2101

ABS catalogue 3222.0

Australian Bureau of

Statistics

Basis of projections for

future demand and cost

scenarios

Medicare Group Reports Medicare Australia Trends in MBS items relating

to administration of blood

and blood products

Red cell utilisation data 2006 SA Health Clinical uses (according to

Diagnostic Related

Groups)and age profile of

red cell use in SA public

hospitals in 2006

A P P E ND I X 4

Persons and Organisations Consulted

Rachel Allden, Department of Health, South Australia

Professor Warwick Anderson AM, National Health & Medical Research Council

Dr Tony Badrick, Pathology Associations Council

Dr Raymond Banh, Mater Childrens' Hospital, Brisbane

Dr Peter Bardy, Adelaide Health Service

Mr Ken Barker, National Blood Authority Board

Julie‐Anne Bates, Australian Red Cross Blood Service

Mr Stephen Begg, Queensland Health

Professor Jim Bishop AO, Department of Health and Ageing

Karen Botting, Department of Health, Victoria

Professor Chris Brook, Department of Health, Victoria

Dr Heather Buchan, National Institute of Clinical Studies, National Health & Medical Research Council

Professor Leslie Burnett, Australasian Association of Clinical Biochemists

Donna Burton, Department of Health and Ageing

Dr Elizabeth Campbell, CSL Limited

Sharon Caris, Haemophilia Foundation Australia

Dr Kevin Carpenter, Human Genetics Society of Australasia

Dr Jill Carstairs, NSW Health

Ray Carty, Department of Health and Ageing

Dr Kerry Chant, NSW Health

Professor John Christadoulou, Human Genetics Society of Australasia

Michaela Coleborne, Department of Health and Ageing

Professor Jamie Cooper, Alfred Hospital, Melbourne

Mr Paul Coulter, CSL Limited

Julie Crowe, Department of Health & Human Services, Tasmania

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Karen Chudleigh, Department of Health and Ageing

Dr Jeff Davies, CSL Limited

Noelene Davies, Australian Red Cross Blood Service

Dr Ken Davis, Royal Adelaide Hospital

Dr David DeLeacy, Queensland Medical Laboratory

Carolyn der Vartanian, Bloodwatch, Clinical Excellence Commission, NSW

Ms Erin Finn, Queensland Health

Dr Jan Fizzell, NSW Health

Dr Peter Flanagan, New Zealand Blood Service

Ms Rosie Forster, National Institute of Clinical Studies, National Health & Medical Research Council

Dr Craig French, Australia and New Zealand Intensive Care Society

Professor Michael Good AO, National Health & Medical Research Council

Dr Peter Graham, Australasian Association of Clinical Biochemists

Peter Graves, Department of Health and Ageing

Ms Stephanie Gunn, National Blood Authority

Ms Bernie Harrison, Bloodwatch, Clinical Excellence Commission, NSW

Dr Michael Harrison, Australian Association of Pathology Practices

Dr Anne Haughton, Sullivan Nicolaides Pathology, Queensland

Dr Bob Heddle, Head of Immunology Directorate, South Australia

Bill Heiler, NSW Health

Dr Chris Hogan, Royal Melbourne Hospital

Dr Matthew Hooper, Emergency Medical Retrieval Service, South Australia

Russell Hunt, Department of Health, South Australia

Susan Ireland, Department of Health, South Australia

Prof James Isbister, Clinical Professor of Medicine, University of Sydney

David Jones, Australian Red Cross Blood Service

Natasha Kearey, Princess Alexandra Hospital

Barny Lee, Department of Health and Ageing

Michael Legg, Health Informatics Society of Australia Ltd

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Ms Meredith Liddy, Australian Institute of Medical Scientists

Sharyn McGregor, Department of Health and Ageing

Dr Katherine Marsden, Royal Hobart Hospital

Mr Andrew Mead, National Blood Authority

Medicare Benefits Division, Department of Health and Ageing

Dr John Merlino, Australian Society for Microbiology

Mr Neville Moller, Australian Association of Pathology Practices

Associate Professor Ray Morris, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

Ms Mary Murnane, Department of Health and Ageing

Jo Murray, Department of Health and Ageing

Glenn Muscat, Department of Health and Ageing

Dr Daniel Owens, Haematology Society of Australia and New Zealand

Ms Krystyna Parrott, Department of Health, South Australia

Dr Louise Phillips, Department of Epidemiology, Monash University

Dr Paddy Phillips, Department of Health, South Australia

Dr Sue Phillips, National Institute of Clinical Studies, National Health & Medical Research Council

Tony Prior, Australasian Association of Clinical Biochemists

Kevin Ratcliffe, Department of Health and Human Services, Tasmania

Dr Kathryn Robinson, Haematologist, South Australia

Penny Rogers, National Coalition of Public Pathology Inc.

Dr Bronwen Ross, Royal College of Pathologists of Australasia

Terry Ryan, Department of Health and Ageing

A/Prof David Roxby, Department of Health, South Australia

Ms Gayle Salkield, Princess Alexandra Hospital

Tony Samsom, Department of Health and Human Services, Tasmania

Dr Helen Savoia, Royal Children’s Hospital, Victoria

Dr Ben Saxon, Women’s and Children’s Hospital, South Australia

Mr Geoff Simon, Queensland Health

Dr Romi Sinha, Department of Health, South Australia

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Dr Andrew Spence, Haematology Society of Australia and New Zealand

Tracey Spiegel, Australian Red Cross Blood Service

Jane Spittle, Department of Health and Ageing

Dr Greg Stewart, NSW Health

Mr Michael Stone, National Blood Authority

Dr Simon Towler, Department of Health, Western Australia

Dr Alison Turner, National Blood Authority

Dr Santosh Verghese, Flinders Medical Centre, South Australia

Therese Verma, Department of Health and Ageing

Dr Craig White, Department of Health and Human Services, Tasmania

Dr Bronwyn Williams, Queensland Health

Ms Jennifer Williams, Australian Red Cross Blood Service

Paul Williams, Endocrine Society of Australia

Associate Professor Vin Williams, Australian Society of Cytology

Associate Professor Roger Wilson, National Coalition of Public Pathology

Dr Erica Wood, Australia and New Zealand Society of Blood Transfusion, and Australian Red Cross Blood Service

Associate Professor Tony Woods, Pathology Associations Council

A P P E ND I X 5

Research References

APPROPRIATE USE OF BLOOD AND BLOOD PRODUCTS

Reference

Isbister, J.P., et al. Adverse Blood transfusion Outcomes: Establishing Causation. Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1‐8 (yet to be published)

Key Findings

Isbister, J.P., et al. point out that because of the already recognised serious hazards of allogeneic transfusion, the Precautionary Principle and ongoing evidence of inappropriate blood transfusion, causation, and not the demand for RCTs should be what drives clinicians and researchers, including those that develop clinical practice guidelines for transfusion. Moreover, there is a challenge in establishing causation between transfusion and adverse outcomes in the absence of, or while awaiting, evidence from large well‐designed and conducted RCTs.

Isbister, J.P., et al. point out that, whilst there is an extensive literature on transfusion alternatives for minimizing allogeneic RBC transfusion, caution is advisable in the use of the term “transfusion alternatives,” as only some are indeed truly alternatives. Patient blood management is regarded by some as an “intervention” and alternative to allogeneic blood transfusion when the real focus in patient blood management is on optimal medical management and standard of care. Timely diagnosis and management of reversible anaemia, meticulous surgical haemostasis, limiting test sampling blood loss, and tolerance of anaemia in haemodynamic stable patients are not “alternatives” to RBC transfusions. On the other hand, the use of autologous transfusion techniques, erythroid stimulating agents, and antifibrinolytics are transfusion alternative interventions that have benefits, but may bring with them hazards that need balancing in the same manner as the decision to transfuse.

Details

In relation to Evidence‐Based Medicine (EBM), the RCT is considered the criterion standard, applying statistical probabilities to arrive at “the truth.” This current view of EBM often fails to acknowledge that most important advances in medicine usually start with clinical observations, and the RCT is but one tool for acquiring knowledge about causation. The EBM classifications of levels of evidence, which invariably give the highest quality ranking to evidence derived from RCTs, are based on probabilistic causation.

As a result, Isbister, J.P., et al. say, it offers only a limited perspective of evidence of causation and efficacy for many of modern medicine's understanding of disease and therapeutic interventions32 33. Observational registry data on tuberculosis and occupational lung disease in Welsh mining villages was collected by Cochrane in the 1950s, who established his reputation as the father of medical registries. Cochrane34 advocated observation before making decisions about underlying causes and possible interventions. Sir Austin Bradford Hill35, often called the father of medical RCTs, established

32 Oxman AD: Checklists for review articles. BMJ 309:648‐651, 1994. 33 Efron BRA: Fisher in the 21st century. Stat Sci 13:95‐122, 1998. 34 Cochrane AL: The detection of pulmonary tuberculosis in a community. Br Med Bull 10:91‐95, 1954. 35 Doll R, Hill AB: The mortality of doctors in relation to their smoking habits: A preliminary report. Br Med J

1:1451‐1455, 1954.

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cigarette smoking as a causative factor for development of lung cancer in a situation where RCTs could never be done. Many similarities exist between cigarette smoking being causative for disease and RBC transfusions contributing to adverse or suboptimal clinical outcomes. Hill36 recognized the problems and limitations of RCTs and proposed nine criteria whose purpose was to address the problem of supporting causation when there is an association, but it is impractical or unethical to conduct RCTs. Such an approach was used in the smoking and lung cancer debate and, more recently, in establishing the causal relationship between asbestos‐related lung disease and mesothelioma37 38. Hill's nine criteria are:

availability of experimental evidence;

strength of association;

temporality;

biological gradient;

biologic plausibility;

coherence;

consistency;

analogy; and

specificity.

Hill emphasised that these criteria are to be considered in deciding if the most likely interpretation of an observed association is a causation; they are not intended to provide indisputable evidence for or against causation, and causation may still exist in absence of one or more of these criteria (except for temporality)39. Several attempts at modifying Bradford Hill's criteria have been made to clarify and simplify their application. Howick et al.40 recently proposed organizing Bradford Hill's criteria into three categories of evidence: direct, mechanistic, and parallel. Table 60 summarises how Bradford Hill's criteria fit within these three categories and illustrates their application to transfusion outcomes. The one exception is Bradford Hill's criteria of specificity, which has been eliminated given that diseases usually have multiple causes and effects and most interventions also have multiple effects. This exclusion of specificity has been proposed by Howick et al.41 in their simplified approach to applying Hill's approach to increasing the probability of causation from observational evidence. This is certainly the case in the clinical circumstance of RBC transfusion and adverse transfusion outcomes.

36 Hill AB: The environment and disease: Association or causation? Proc R Soc Med 58:295‐300, 1965. 37 Doll R, Hill AB: Lung cancer and other causes of death in relation to smoking: A second report on the mortality of British doctors. Br Med J 2:1071‐1081, 1956. 38 Kannerstein M, Churg J, McCaughey WT: Asbestos and mesothelioma: A review. Pathol Annu 13(Pt 1):81‐129. 39 Brown MS, Goldstein JL: Koch's postulates for cholesterol. Cell 71:187‐188, 1992. 40 Howick J, Glasziou P, Aronson JK: The evolution of evidence hierarchies: What can Bradford Hill's ‘guidelines for causation’ contribute? J R Soc Med 102:186‐194, 2009. 41 Howick J, Glasziou P, Aronson JK: The evolution of evidence hierarchies: What can Bradford Hill's ‘guidelines

for causation’ contribute? J R Soc Med 102:186‐194, 2009.

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TABLE 60: BRADFORD HILL CRITERIA MODIFIED INTO GUIDELINES42 THAT SUPPORT CAUSATION WHEN AN ASSOCIATION IS PRESENT

Source: Isbister Adverse Blood transfusion Outcomes: Establishing Causation. Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1-8 (yet to be published)

42 Howick J, Glasziou P, Aronson JK: The evolution of evidence hierarchies: What can Bradford Hill's ‘guidelines

for causation’ contribute? J R Soc Med 102:186‐194, 2009.

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It is not questioned that allogeneic blood transfusions have risks and can cause serious adverse events. However, notwithstanding the cases of profound anaemia and haemorrhage with impaired oxygen delivery to tissues, Isbister, J.P., et al. argue that in most patients who are currently considered to be transfusion candidates, blood transfusions do not improve the outcomes and, conversely, cause worse clinical outcomes. The evidence comes from a multitude of mostly observational studies comparing the outcomes of transfused and not transfused patients in various common clinical settings. Subjecting observational data to Bradford Hill criteria can help strengthen the case for a causal relationship.

From the patient's perspective, the primary responsibility of clinicians is to manage the patient's own blood as a precious and unique resource that should not be wasted and to only consider allogeneic blood component therapy when there is no other option – the so‐called new paradigm in transfusion practice – Patient Blood Management (see further discussion below). The Isbister, J.P., et al. review, addressing issues surrounding the safety and efficacy of RBC transfusions for treating anaemia, challenges the dogmas long embedded in clinical practice regarded as standard of care. Central to problem‐based transfusion medicine, in relationship to RBC transfusions, are the diagnosis and management of anaemia. Anaemia is common and generally poorly managed despite good scientific understanding of mechanisms and sophisticated diagnostic methods (see further discussion elsewhere in this Report on this topic in relation to inappropriate transfusion practice). In most circumstances, anaemia is mild, and its significance per se in terms of impacting adversely on clinical outcomes in the absence of confounding co morbidities is questionable. Although there is literature associating anaemia with poorer outcomes in some circumstances, there is no good evidence that RBC transfusions improve the outcomes.

Isbister, J.P., et al. point out that, whilst there is an extensive literature on transfusion alternatives for minimizing allogeneic RBC transfusion, caution is advisable in the use of the term “transfusion alternatives,” as only some are indeed truly alternatives. Patient blood management is regarded by some as an “intervention” and alternative to allogeneic blood transfusion when the real focus in patient blood management is on optimal medical management and standard of care. Timely diagnosis and management of reversible anaemia, meticulous surgical haemostasis, limiting test sampling blood loss, and tolerance of anaemia in haemodynamic stable patients are not “alternatives” to RBC transfusions. On the other hand, the use of autologous transfusion techniques, erythroid stimulating agents, and antifibrinolytics are transfusion alternative interventions that have benefits, but may bring with them hazards that need balancing in the same manner as the decision to transfuse. The hazards of autologous transfusion are also set out in the NSW CEC Blood Program Myth Buster Poster 443: Autologous blood (pre‐donated) is risk‐free, which says that, “… Pre‐donated autologous transfusion is not risk‐free and there are a variety of adverse events associated with this practice.”

Although their review focuses on the risks and benefits of RBC transfusions in anaemic haemodynamically stable patients without co morbidities, Isbister, J.P., et al. acknowledge that the use of transfusion alternatives demands similar attention to the benefits and safety. However, it is important that, when balancing all the options, it should be done on a “level playing field” and RBC transfusion should no longer be regarded as the default and “safe” option when there is clinical uncertainty.

Isbister, J.P., et al. postulate that a compelling case for applying the precautionary principle to transfusion medicine existed long before RBC transfusions were implicated as a general risk factor

43 NSW Clinical Excellence Commission (CEC) Blood Watch Program. Myth Buster Poster 4: Autologous blood (pre‐donated) is risk‐free. On the CEC Blood Watch Program website (accessed on 23 February 2011) at: http://www.cec.health.nsw.gov.au/programs/blood‐watch/myths

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for adverse clinical outcomes. The “tissue transplant” of blood transfusion has always been a potentially hazardous therapeutic intervention, with numerous clearly understood complications, some avoidable, but many not. As advocated by Beale, “Blood transfusion is like marriage: it should not be entered upon lightly, unadvisedly or wantonly, or more often than is absolutely necessary44”. The recognized hazards of allogeneic blood transfusion aside, the case for a precautionary approach is strengthened further with the possible, and now probable, recognition that transfusions are a risk factor for adverse clinical outcomes.

A general change in transfusion medicine practice is urgently needed say Isbister, J.P., et al.. Neither the quality and safety issues nor the economic implications can continue to be ignored awaiting the results of RCTs currently in progress or may never be possible45 46 47. Waiting for levels of evidence demanded by Frequentist outcome–focused epidemiology is no longer advisable and may be exposing patients to harm. Bradford Hill himself noted; “All scientific work is incomplete whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. This does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time48.”

Political, financial, and ethical considerations inevitably play a part in decision making in the blood sector; however, there are undeniable reasons why there should be greater focus on the precautionary principle on the demand side of transfusion medicine. It is difficult to understand why this change has met resistance from some clinicians and players in the blood sector. Delaying actions until harm is proven in the context of questionable efficacy would not be acceptable in other areas of medical practice, and we believe that blood transfusion should be treated similarly. Support for adopting a precautionary approach to the transfusion of labile blood components includes the following:

The evidence for efficacy of many blood components in a range of clinical settings, especially in relationship to haemodynamically stable perioperative patients (a large group of blood recipients), is questionable or non‐existent. Randomized controlled trials of a restrictive RBC transfusion policy have confirmed that restrictive transfusion policies are safe and reduce adverse outcomes49 50;

Inappropriate RBC transfusion practices, contrary to guidelines, persist51, and as demonstrated extensively elsewhere in this Report;

Benchmarking studies have identified a wide variation in RBC transfusion practices between countries, hospitals, and individual clinicians52, and as demonstrated extensively elsewhere in this Report;

44 Beale R: The rational use of blood. ANZ J Surg 46:309‐313, 1976. 45 Nowak R: Blood doesn't always save lives. New Sci :8‐9, 2008. 46 Shander A, Hofmann A, Gombotz H, et al.: Estimating the cost of blood: Past, present, and future directions. Best Pract Res Clin Anaesthesiol 21:271‐289, 2007. 47 Blumberg N: Allogeneic transfusion and infection: Economic and clinical implications. Semin Hematol 34(3 Suppl 2):34‐40, 1997. 48 Hill AB: The environment and disease: Association or causation? Proc R Soc Med 58:295‐300, 1965. 49 Hebert PC, Wells G, Blajchman MA, et al.: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 340:409‐417, 1999. 50 Lacroix J, Hebert PC, Hutchison JS, et al.: Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 356:1609‐1619, 2007. 51 Jackson GN, Snowden CA, Indrikovs AJ: A prospective audit program to determine blood component transfusion appropriateness at a large university hospital: A 5‐year experience. Transfus Med Rev 22:154‐161, 2008.

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More appropriate and alternative therapies and interventions are available to avoid or minimize the use of allogeneic blood components53 54;

Implementation of patient blood management is a quality and safety measure that could lead to substantial cost savings55 56 57, and as demonstrated elsewhere in this Report.

Apart from recommending the implementation of patient blood management approaches, Isbister, J.P., et al. concluded that, “ … it is no longer acceptable to maintain a laissez faire approach and assume the benefits and accept the risks of allogeneic blood transfusion. Evidence has accumulated questioning RBC transfusion efficacy and establishing transfusion as a contributing risk factor for adverse clinical outcomes in many clinical settings. Acknowledging that most available data are observational and that rigorous evidence to establish risks and benefits is needed, we should no longer accept transfusions as the default decision when there is clinical uncertainty.”

Reference

Pendergrast, J. M., Sher, G. D. and Callum, J. L. (2005), Changes in intravenous immunoglobulin prescribing patterns during a period of severe product shortages, 1995–2000. Vox Sanguinis, 89: 150–160.

Key Findings

The study concluded that IVIg shortages were followed by a decrease in the number of single‐use recipients, who probably represented empirical use of IVIg, but that this had little effect on the total amount of IVIg distributed annually. Stricter adherence to currently available published recommendations may not be the optimal means of controlling IVIg use within an academic hospital setting. Rather, emphasis may be better placed on improving the evidence base upon which these recommendations are made, for example by conducting controlled prospective clinical trials.

Details

This study noted that Canadian consumption of intravenous immunoglobulin (IVIg) had increased dramatically since it was first marketed in the early 1980s, and Canada had become the world's largest per capita consumer. During the late 1990s, worldwide product shortages of IVIg occurred and this study was designed to identify the disease conditions for which IVIg was being prescribed in academic hospitals during this period, and to explore the effects that IVIg shortages had on prescribing patterns.

Blood bank and pharmacy records of IVIg distribution were collected retrospectively from four Toronto teaching hospitals for the period 1995–2000. These records were then cross‐referenced with patient medical records to determine the indication for IVIg administration. The results were derived from a total of 100,208g of IVIg prescribed to 429 patients over a 6‐year period. Most of the IVIg consumption was in patients with haematological (22%) or neurological (20%) conditions, in recipients of bone marrow transplants (19%) and in patients with infectious disease‐related

52 Gombotz H, Rehak P, Shander A, et al.: Blood use in elective surgery: The Austrian benchmark study. Transfusion 47:1468‐1480, 2007. 53 Goodnough LT, Shander A: Blood management. Arch Pathol Lab Med 131:695‐701, 2007. 54 Pape A, Habler O: Alternatives to allogeneic blood transfusions. Best Pract Res Clin Anaesthesiol 21:221‐239, 2007. 55 Murphy GJ, Reeves BC, Rogers CA, et al.: Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 116:2544‐2552, 2007. 56 Reeves BC, Murphy GJ: Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery. Curr Opin Anaesthesiol 21:669‐673, 2008. 57 Shander A, Hofmann A, Gombotz H, et al.: Estimating the cost of blood: Past, present, and future directions.

Best Pract Res Clin Anaesthesiol 21:271‐289, 2007.

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conditions (including congenital and acquired hypogammaglobulinaemia, 18%). Dermatological conditions (7%) were the most rapidly growing indication for IVIg usage during the 6‐year period of review, increasing from 0% of annual IVIg usage in 1995 to 16% in 2000. Over 80% of the diseases treated were supported by published recommendations. After 1997 there was an abrupt decline in the annual number of patients treated, primarily owing to a decline in single‐use recipients. Annual consumption of IVIg, however, remained stable.

The authors concluded that IVIG shortages were followed by a decrease in the number of single‐use recipients, who probably represented empirical use of IVIg, but that this had little effect on the total amount of IVIg distributed annually. Stricter adherence to currently available published recommendations may not be the optimal means of controlling IVIg use within an academic hospital setting. Rather, emphasis may be better placed on improving the evidence base upon which these recommendations are made, for example by conducting controlled prospective clinical trials.

Reference

Guzick, D.S., On the Same Page: Saving blood, saving money and saving lives. UF Shands Health System website (www.health.ufl.edu/OntheSamePage/), 1 October 2010.

Key Findings

In an unprecedented move the Senior Vice President, Health Affairs and President, UF Shands Health System, in “On the Same Page: Saving blood, saving money, saving lives”, 1 October 2010 wrote to all his staff about the risks, costs, adverse events and benefits associated with transfusion. The article is compelling in relation to the need to change transfusion practice for the benefit of patients and health institutions. It is reproduced in full below.

Details

“You’ve heard it before, but it bears repeating: Quality patient care is our first and most essential focus. Now imagine a procedure performed about 15 million times per year in U.S. hospitals that increases the likelihood of death by 70% and the risk of infection by about 80%, and is associated with other complications such as acute respiratory distress syndrome.

This procedure, performed at an annual cost of $10 billion to $15 billion, is blood transfusion. It is the single most commonly coded procedure for hospital discharges in the United States, according to the Agency for Healthcare Research and Quality.

Interviews with several of our own faculty suggest that improving the quality of care for our patients by developing literature‐based protocols for blood transfusion and reducing adverse events is good medicine. And it also saves money.

So we’ve gathered a team of physicians, nurses and laboratory staff to develop common protocols to ensure an evidence‐based approach to blood product transfusion. In Gainesville, this team will be led by Marc Zumberg, M.D., an associate professor of medicine, and Philip Efron, M.D., an assistant professor of surgery and anaesthesiology. In Jacksonville, the team leaders will be David Wolfson, M.D., an assistant professor of pathology and laboratory medicine, and Agnes Aysola, M.D., an assistant professor of pathology and laboratory medicine.

Each year, approximately 28,000 units of red blood cells are transfused at Shands at UF, and about 11,000 units at Shands Jacksonville. Although the direct cost of each unit of blood is about $175, the total cost is much greater.

After precisely mapping all diagnostic, therapeutic, technical, laboratory, logistic, administrative and informational activities involved in the transfusion of blood in real‐world surgical settings,

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researchers constructed an activity‐based cost model capturing all the actual direct and indirect costs of acquiring, delivering, administering and monitoring red blood cell transfusions from the hospital perspective. (Transfusion 2010; 50:753‐65) This yielded an estimate of $520 to $1,180 for the total cost per unit of blood that reflects the complexities of real‐world blood utilization, depending on the circumstances surrounding the transfusion.

Even if the average were at the low end (e.g., $600 per unit), a reduction of only 10% across Shands at UF and Shands Jacksonville (i.e., about 4,000 units) would save $2.4 million per year.

Achieving such a reduction is a realistic goal. According to data from the University Health System Consortium, which consists of 93 peer institutions, use of red blood cell units by Shands at UF per annual inpatient discharges is 0.87. When UHC hospitals are sorted by numbers of inpatient discharges, all hospitals of our size or larger have lower rates of red blood cell use. For example, the rates for Barnes‐Jewish (Washington University), Vanderbilt University and University of Arizona are 0.68, 0.64 and 0.56, respectively.

In addition, data reported to UHC indicate an annual use of 13,500 units of plasma by Shands at UF and 8,200 units by Shands Jacksonville. Plasma is the liquid part of the blood in which the blood cells are suspended. Plasma for transfusion is usually termed fresh‐frozen plasma, or FFP. FFP is commonly used for a wide variety of indications, but review of the literature would suggest that the evidence favours plasma transfusion in only a very limited number of clinical situations.

Specifically, a recent report from a blue‐ribbon multidisciplinary guidelines panel (Transfusion 2010;50:1227‐1239), which conducted a systematic review and meta‐analysis of randomized and observational studies, concluded that FFP was indicated in patients with blood loss requiring massive transfusion and in patients with warfarin therapy in association with intracranial haemorrhage. The panel did not favour plasma transfusion for other selected groups of patients.

Other opportunities become apparent after reviewing the contemporary medical literature and listening to our haematology faculty’s expert judgments. For example, it is still common practice to attempt to correct “abnormal” laboratory values of haemostasis prophylactically in patients with liver disease by administering blood products. But a recent review of the literature suggests that such a practice is not supported by the evidence. Thanks to tremendous progress in the understanding of haemostatic function in patients with liver disease, the long‐standing dogma that patients with liver disease have a bleeding tendency that can be corrected by transfusion no longer appears to be supported by data from both clinical and laboratory studies (Blood 2010;116:878‐885). Rather, it appears that attempts at preoperative transfusion in patients with liver disease does not reduce, and may in fact promote, bleeding.

A recent review in Critical Care Medicine classified 45 studies including 272,596 patients as 1) risks outweigh benefits, 2) neutral risk and 3) benefits outweigh risks. In 42 of 45 studies, the risks of red blood cell transfusion outweighed the benefits, the risk was neutral in two studies, and the benefits outweighed the risks in a single subgroup of a single study (elderly patients with an acute heart attack and a hematocrit less than 30%.

Still, blood transfusion can be a life‐saving procedure for many patients in specific situations involving haemorrhage from trauma or surgery, or in many cases of severe anaemia in patients who are critically ill. The data are quite sobering, however. As suggested in an editorial by Drs Howard Corwin and Jeffrey Carson (NEJM 2007;356:1667‐8): "Red‐cell transfusion should no longer be regarded as “may help, will not hurt” but, rather, should be approached as “first, do no harm.’”

Yet over the past several decades, with the exception of concern about transfusion‐related infection that has been largely eliminated thanks to effective testing for hepatitis and HIV, the practice of transfusion has grown dramatically under the "may help, can't hurt" mindset.

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In 1999, the results of an important clinical trial, Transfusion Requirements in Critical Care, were reported (NEJM 1999;340:409‐17). In this randomized, controlled study involving critically ill adults, a liberal strategy (transfuse if the haemoglobin level drops below 10.0 g/dL) was compared with a restrictive strategy (transfuse if haemoglobin drops below 7.0 g/dL). Patients randomly assigned to restrictive management received 54% fewer red‐cell units than did the liberal management group, and the restrictive strategy was found to be at least as effective as the liberal strategy with respect to mortality. In patients who were less acutely ill or under 55 years of age, the restrictive strategy was actually superior, in that compared with the liberal strategy it was associated with lower mortality.

A study of children in a Pediatric Intensive Care Unit (NEJM 2007;365:1609‐19) reached similar conclusions. Using multiple organ dysfunctions as an endpoint, a restrictive transfusion strategy was at least equivalent to the liberal strategy in this outcome, and was associated with a 44% reduction in the number of red‐cell transfusions.

These findings come at a time when a quarter of a century of research demonstrates that transfused patients, in general, have much poorer outcomes than similar untransfused patients, and that patients who receive more transfusions do progressively worse in a dose‐dependent fashion (Transfusion 2005 45[Supplement]: 33S‐40S).

More recent studies reveal that among patients who are treated for trauma, blood transfusion increases pneumonia, acute respiratory distress syndrome and mortality (J. Trauma 2005, 59:19‐23). Among burn patients, blood transfusions increase mortality and infection, controlling for indices of burn severity (Crit Care Med 2006, 34:1602‐9).

The history of blood transfusion is intertwined with the history of medicine generally, and is one of the great examples of true translational science. The first successful transfusion of human blood was performed by Dr James Blundell, a British obstetrician, who treated a woman who developed postpartum haemorrhage using her husband's blood. Through the 1800s, transfusions were only infrequently performed (e.g., to treat conditions such as haemophilia), as many recipients died due to what we now know were haemolytic reactions from blood group incompatibility.

The ABO blood group system was discovered by the Austrian Karl Landsteiner, M.D., in 1901 (for which he won the Nobel Prize in Medicine or Physiology in 1930), providing the scientific basis for improving the safety of blood transfusion. In 1939, Drs Landsteiner, Levine and Weiner discovered the Rh blood group system. In 1961, Rh immune globulin was commercially introduced to prevent Rh disease in newborns of Rh‐negative women.

Since then, advances have occurred in the systems of infection screening, storage, distribution and processing of blood products. Currently accepted blood transfusion practices evolved prior to the concepts of randomized trials and clinical outcomes studies, however, and developed all the sanctity expected of time‐honoured therapies.

In summary, interviews with faculty involved in blood transfusion suggest a consensus: As is often the case in quality improvement initiatives, improving the quality of care for our patients by developing literature‐based protocols for blood transfusion and reducing adverse events will also result in cost savings. I would add, in the spirit of the goals of our Clinical and Translational Science Award, that research on blood transfusion has progressed through the first two translational stages: from "T1" (discovery of blood groups, fractionation and storage methods, etc., translated to individual patient treatment), to "T2" (defining risk groups and haemoglobin targets for translation to optimal clinical practice).

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It is now time to progress to the "T3" phase, in which accumulated knowledge on best practices can be disseminated to our physicians, nurses and students, so that known best practices can be achieved across our health‐care system in a manner that saves blood, saves money and saves lives.

Forward Together,

David S. Guzick, M.D., Ph.D.”

Reference

Morton, J., et al., Frequency and outcomes of Blood Products Transfusion Across Procedures and Clinical Conditions Warranting Inpatient Care: An Analysis of the 2004 Healthcare Cost and Utilization Project National Inpatient Sample Database. Americal Journal of Medical Quality, 2010. 25:289: p. 289‐296.

Key Findings

Patient discharges in the transfused cohort were significantly more likely to have at least one co morbidity than discharges in the non‐transfused cohort (54.5% compared to 47.1%). Of the estimated 38.66 million discharges in the United States in 2004, 5.8% (2.33 million) were associated with blood products transfusion. Average length of stay was 2.5 days longer, odds of death were 1.7 times higher, and odds of infection 1.9 times higher for the transfused cohort.

Despite limitations, this study shows that more than 2 million hospital admissions annually are associated with a blood products transfusion and that patients remain at risk of experiencing adverse clinical outcomes. The observation that transfusion recipients experience negative outcomes independent of age, sex, co morbidities, admission type, or DRG assignment warrants further investigation to better identify the appropriateness of current transfusion triggers and to develop and implement more effective approaches to reduce the non‐emergent use of blood in hospitalized patients. Additional research to identify transfusion triggers, including patient severity, risk–benefit trade‐offs, and the use of blood in elective surgical cases, should be a priority. In a significant number of trauma and urgent cases when uncontrolled haemorrhage is the clinical priority, surgeons often have limited options to rapidly correct blood loss, and therefore, the threshold for transfusion may be low. However, with elective cases, surgeons are likely to have more options such as the use of haemostatic agents to address blood loss and avoid or reduce the need for transfusion. This is especially important given the persistent challenges associated with maintaining an adequate blood supply. TRALI and incompatibility reactions were not reported for patients identified as transfusion recipients. This finding also warrants further investigation, given that the Joint Commission and the American Association of Blood Banks have established transfusion‐specific performance improvement standards, blood use reviews, and reporting requirements for suspected transfusion‐related adverse events. Finally, given that transfusion‐related adverse clinical and health‐related quality‐of‐life outcomes may persist after hospital discharge, additional prospective observational studies are needed to assess the long‐term health status and quality of life of transfusion recipients. In conclusion, raising provider awareness and recognition of the frequency and potential negative clinical outcomes of blood products transfusion—as an independent predictor or surrogate for blood loss—may yield significant clinical and quality‐of‐life benefits at the individual patient level. Equally important is the need to encourage providers to adopt strategies and techniques that are more effective at controlling inadequate surgical haemostasis and that may reduce the frequency of blood products transfusions.

Details

The objective of a very large retrospective cohort study in 2004 in the US, Morton, et al., was to enumerate the national frequency of blood products transfusion and associated clinical and health

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outcomes across the full spectrum of procedures and clinical conditions warranting inpatient care. To the best of our knowledge, no study to date has assessed this. This information is important for many reasons, including the following:

increasing provider and patient awareness;

encouraging the adoption of novel approaches to minimize intraoperative and early

postoperative bleeding, reducing blood transfusions; and

most important, improving postoperative outcomes and health‐related quality of life.

In this study, the frequency of blood products transfusion, morbidity, mortality, length of stay (LOS), and hospital charges were examined among all hospitalisations (discharges) in the United States in 2004 using the Agency for Healthcare Research and Quality’s 2004 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) (Table 61). The NIS is an all‐payer national survey that approximates a 20% multistage sample of inpatient care in the United States. Included in NIS are US community hospitals, which are defined by the American Hospital Association to be “all non‐federal, short‐term, general, and other specialty hospitals.” Facilities excluded from NIS are: short‐term rehabilitation facilities, long‐term hospitals, psychiatric hospitals, alcoholism/chemical dependency treatment facilities, and federal facilities (e.g., Veterans Administration hospitals). The final sample for NIS 2004 was drawn from 37 states and includes patient‐level data for 8,004,571 discharges from 1004 hospitals. Only inpatient data found in a discharge abstract are available in the NIS, with safeguards to protect the privacy of individual patients, physicians, and hospitals. The NIS does not have unique patient identifiers, and as a result, patients cannot be followed longitudinally. The NIS includes more than 100 clinical and nonclinical data elements for each hospitalization including patient demographics, one principal and up to 14 secondary diagnoses, one principal and up to 14 secondary procedures, admission and discharge status, LOS, primary payer source, total charges, and hospital characteristics.

TABLE 61: TOP 10 PRIMARY PROCEDURE CATEGORIES WITH GREATEST FREQUENCY OF TRANSFUSION

Source: Morton, J., et al., Frequency and outcomes of Blood Products Transfusion Across Procedures and Clinical Conditions Warranting Inpatient Care: An Analysis of the 2004 Healthcare Cost and Utilization Project National Inpatient Sample Database. American Journal of Medical Quality, 2010.

The following outcomes in this Morton, et al. study were evaluated: in‐hospital mortality, LOS, postoperative infections, non‐infectious transfusion related complications, and total charges. ICD‐9‐CM diagnosis codes were used to identify postoperative infections and included the following: bacteraemia (790.7), cellulitis and abscess (682), mediastinitis (519.2), osteomyelitis (730.0, 730.2,

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and 730.9), pneumonia (481, 482, 485, and 486), septicaemia (038), and urinary tract infection (599.0). ICD‐9‐CM diagnosis codes were also used to identify non‐infectious transfusion‐related complications including TRALI (518.7), anaphylactic shock caused by serum (999.4), other serum reaction (999.5), ABO incompatibility reaction (999.6), and Rh incompatibility reaction (999.7). Additional complications were examined separately from these because they capture non‐transfusion‐related events in addition to events related to transfusion; thus, the best estimate of transfusion‐related complications falls somewhere in between. These included air embolism (999.1), other vascular complications (999.2), other infection (999.3), and transfusion reaction not otherwise specified (999.8).

According to the 2004 NIS database, there were an estimated 38.66 million discharges in the United States in 2004. Approximately 5.8% (2.23 million) of these discharges recorded an ICD‐9‐CM procedure code for blood products transfusion. The 10 most common CCS categories for procedures performed during the same hospitalization as a transfusion accounted for approximately 10% of all hospitalizations and more than 35% of hospitalizations in the transfused cohort. Among transfusion recipients, the most common orthopaedic, cardiovascular, and colorectal procedures made up 13.7%, 7.2%, and 4.3%, respectively. Hip replacement was the most common procedure associated with transfusion (Figure 103 below), with more than one quarter (29.8%) of discharges from hip replacement requiring transfusion. Blood products transfusion was also associated with more than 20% of discharges involving each of the following procedures: repair of a fractured or dislocated hip and femur (27.1%), CABG surgery (24.9%), upper gastrointestinal endoscopy with biopsy (22.5%), and knee arthroplasty (20.6%).

FIGURE 103: FREQUENCY OF TRANSFUSION AMONG TOP 10 PROCEDURES WITH GREATEST FREQUENCY OF TRANSFUSION

Source Morton, J., et al., Frequency and outcomes of Blood Products Transfusion Across Procedures and Clinical Conditions Warranting Inpatient Care: An Analysis of the 2004 Healthcare Cost and Utilization Project National Inpatient Sample Database. American Journal of Medical Quality, 2010. 25:289: p. 289-296

Blood products transfusion was also associated with more than 20% of discharges involving each of the following procedures: repair of a fractured or dislocated hip and femur (27.1%), CABG surgery (24.9%), upper gastrointestinal endoscopy with biopsy (22.5%), and knee arthroplasty (20.6%).

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The overall average age of the discharges was 61.1 years; 44.7% were male. On average, patients who received blood products transfusion were older (mean 66.9 years) in the transfused cohort compared with the non‐transfused cohort (59.7 years; P < .0001). Almost half (48.5%) of patient discharges were associated with at least 1 co morbidity. Patient discharges in the transfused cohort were significantly more likely to have at least one co morbidity than discharges in the non‐transfused cohort (54.5% vs. 47.1 %; P < .0001). Overall, almost one third (29.1%) had private insurance and two thirds (64.3%) had public insurance. Additionally, 72.6% were designated as emergent or urgent.

Average LOS, mortality, and postoperative infection rates were significantly higher in the transfused cohort than in the non‐transfused cohort. Average LOS was 2.5 days longer for the transfused cohort compared with the non‐transfused cohort after adjusting for confounders (P < .0001). Additionally, total charges were $17,194 higher for the transfused cohort compared with the non‐transfused cohort after adjusting for confounders (P < .0001). Overall, death occurred in 2.1% of all hospitalizations in 2004 and in 6.4% of the 10 procedure categories most associated with transfusion. Odds of death were 1.7 times higher in the transfused cohort compared with the non‐transfused cohort after controlling for age, sex, Charlson co morbidity index, admission type, and DRG (P < .0001). The infection rate was also significantly higher for the transfused cohort compared with the non‐transfused cohort (0.33% vs. 0.15%; P < .0001;.

After controlling for confounders, the odds of having at least one postoperative infection was 1.9 times greater for the transfused cohort than for the non‐transfused (P < .0001). The most frequently recorded postoperative infection was pneumonia, whose frequency was 0.12% in the transfused cohort compared with 0.06% in the non‐transfused cohort (P < .0001). No discharges with an ICD‐9‐CM diagnosis code indicating the occurrence of a non‐infectious complication of transfusion were identified among the transfused cohort. Minor events may not have been coded in NIS.

TABLE 62: DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF INPATIENT STAYS AMONG TOP 10 PROCEDURES WITH GREATEST FREQUENCY OF TRANSFUSION

Source Morton, J., et al., Frequency and outcomes of Blood Products Transfusion Across Procedures and Clinical Conditions Warranting Inpatient Care: An Analysis of the 2004 Healthcare Cost and Utilization Project National Inpatient Sample Database. American Journal of Medical Quality, 2010. 25:289:

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TABLE 63: OUTCOMES ASSOCIATED WITH BLOOD TRANSFUSION IN HOSPITALIZED PATIENTS AMONG TOP 10 PROCEDURES WITH GREATEST FREQUENCY OF TRANSFUSION

Source Morton, J., et al., Frequency and outcomes of Blood Products Transfusion Across Procedures and Clinical Conditions Warranting Inpatient Care: An Analysis of the 2004 Healthcare Cost and Utilization Project National Inpatient Sample Database. American Journal of Medical Quality, 2010. 25:289:

There are several limitations to this study. First, this analysis is based on identifying blood products transfusion recipients using ICD‐9‐CM procedure codes that indicate the occurrence of transfusion. For reasons discussed previously, transfusion procedure codes are likely to be underreported. As such, all relevant cases may not have been captured, which would underestimate the true frequency of blood products transfusion in hospitalized patients, affect demographic composition of the study population, and influence other outcome measures of interest such as LOS, postoperative infection rates, and mortality. However, given the extensive sample size, the magnitude and direction of the results reported here are robust, even with the potential for underreporting or misclassification of some transfusion cases.

Second, only data collected in the 2004 NIS database were assessed; these are derived from discharge record abstractions. Thus, detailed and precise information was not available to validate that a blood products transfusion procedure was performed or that a patient actually experienced a negative outcome. Also, cross‐sectional survey databases such as NIS do not provide preadmission or post‐hospital discharge data. Without these additional data, the nature or severity of blood loss, specific trigger for transfusion, number of units transfused, patient selection bias for endoscopic versus open approach, or link between procedure and timing of transfusion, for example, preoperative, intraoperative, or postoperative, cannot be accurately determined.

Third, autologous is often considered to be a safer blood product with respect to compatibility reactions; however, it still carries the risks of inflammatory reaction and infection associated with any transfusion. Perioperative autologous transfusion that would largely be a cell saver product may be used extensively in orthopaedic and cardiac procedures and make up a significant portion of the blood products transfusion represented in this study. The negative outcome rates in this study may

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be conservatively low because of the inclusion of the large number of orthopaedic and cardiac procedures.

Despite these limitations, this Morton, et al. study shows that more than 2 million hospital admissions annually are associated with a blood products transfusion and that patients remain at risk of experiencing adverse clinical outcomes. The observation that transfusion recipients experience negative outcomes independent of age, sex, co morbidities, admission type, or DRG assignment warrants further investigation to better identify the appropriateness of current transfusion triggers and to develop and implement more effective approaches to reduce the non‐emergent use of blood in hospitalized patients. Additional research to identify transfusion triggers, including patient severity, risk–benefit trade‐offs, and the use of blood in elective surgical cases, should be a priority. In a significant number of trauma and urgent cases when uncontrolled haemorrhage is the clinical priority, surgeons often have limited options to rapidly correct blood loss, and therefore, the threshold for transfusion may be low. However, with elective cases, surgeons are likely to have more options such as the use of haemostatic agents to address blood loss and avoid or reduce the need for transfusion. This is especially important given the persistent challenges associated with maintaining an adequate blood supply. TRALI and incompatibility reactions were not reported for patients identified as transfusion recipients. This finding also warrants further investigation, given that the Joint Commission and the American Association of Blood Banks have established transfusion‐specific performance improvement standards, blood use reviews, and reporting requirements for suspected transfusion‐related adverse events. Finally, given that transfusion‐related adverse clinical and health‐related quality‐of‐life outcomes may persist after hospital discharge, additional prospective observational studies are needed to assess the long‐term health status and quality of life of transfusion recipients. In conclusion, raising provider awareness and recognition of the frequency and potential negative clinical outcomes of blood products transfusion—as an independent predictor or surrogate for blood loss—may yield significant clinical and quality‐of‐life benefits at the individual patient level. Equally important is the need to encourage providers to adopt strategies and techniques that are more effective at controlling inadequate surgical haemostasis and that may reduce the frequency of blood products transfusions.

Reference

Holzer, BR, Egger M, Teuscher T, Koch S, Mboya DM, Smith GD. Childhood anaemia in Africa: to transfuse or not transfuse? Acta Trop 1993;55:47‐51

Bojang KA, Palmer A, Boele van Heensbroek M, Banya WA, Greenwood BM. Management of severe malarial anaemia in Gambian children. Trans R Soc Trop Med Hyg 1997;91:557‐61

Meremikwu M, Smith HJ. Blood transfusion for treating malarial anaemia. Cochrane Database Syst Rev 2000:CD)001475

Key Findings

Children with severe malaria anaemia received either malarial treatment and whole blood transfusion or malaria treatment alone. There was no significant difference between the transfused and non‐transfused groups although there were significantly more adverse events in the transfused group compared with the non‐transfused group.

Details

In two African randomized controlled trials (RCT), Holzer et al. randomised 116 children (aged 2 months to 6 years) with severe malarial anaemia (Hb level between 40 g/L and 57 g/L) to receive either malaria treatment and whole blood transfusion (relatively fresh blood donated by relatives), or malaria treatment alone. Bojang et al. randomised 114 children (aged 6 months to 9 years) with

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severe malarial anaemia (Hb level between 40 g/L and 50 g/L) to receive either whole blood transfusion or oral iron. Meremikwu and Smith combined the data from these two trials in a Cochrane Collaboration review and meta‐analysis. The combined data showed there was no significant difference in mortality between the transfused and non‐transfused (RR 0.41; 95% CI, 0.06‐2.70; p=0.4). There were, however, significantly more severe adverse events in the transfused group compared with the non‐transfused group (RR 8.60; 95% CI, 1.11‐ 66.43; P=0.04).

Reference

Taylor RW et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med 2006 July 34(9): 2302‐2308

Key Findings

Taylor et al. identified transfusion being associated with an adjusted dose‐dependent increased risk of nosocomial infection (NI), ICU and hospital length of stay and mortality in 2085 surgical and medical ICU patients. Transfused patients were 6 times more likely to develop infection compared with non‐transfused. The authors stated, “Transfused patients with a better prognosis had higher mortality rates, suggesting that transfusions may do more harm than good in ICU patients who have a reasonably good chance of survival.”

Details

Taylor et al. identified transfusion being associated with an adjusted dose‐dependent increased risk of nosocomial infection (NI), ICU and hospital LOS and mortality in 2085 surgical and medical ICU patients. Compared with non‐transfused patients, the transfused had higher NI rates (14.3% vs. 5.8%; P<.0001), longer ICU LOS (8.2 vs. 3.3 days; P<.0001), longer hospital LOS (18.3 vs. 9.9 days; P<.0001) and higher mortality rates (21.8% vs. 10.2%; P<.0001). Transfused patients were 6 times more likely to develop infection compared with non‐transfused. The investigators documented a dose‐dependent relationship with the risk of developing infection increasing by 9.7% for every red blood cell unit transfused. Even after adjusting for survival probability, transfused patients had significantly higher NI rates (14.3% vs. 5.8%; P<.0001), longer ICU LOS (8.2 vs. 3.3 days; P<.0001), longer hospital LOS (18.3 vs. 9.9 days; P<.0001), and higher mortality rates (21.8% vs. 10.2%; P<.0001). A sobering finding was after adjusting for patients’ probability of survival (POS), based on Mortality Prediction Model scores, transfused patients who were less severely ill (higher POS quartiles) had significantly higher mortality rates than similar POS non‐transfused patients. The authors stated, “Transfused patients with a better prognosis had higher mortality rates, suggesting that transfusions may do more harm than good in ICU patients who have a reasonably good chance of survival.” Leucoreduction resulted in non‐significant reduction in NI in this study. The authors also discussed the possible clinical implications of this finding. The cost of NI in the US is estimated to be greater than US$2 billion per annum and worldwide adding US$1,000‐4,500 extra cost per patient in ICU from one NI. Bloodstream infections can average $40,000 per survivor.

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FIGURE 104: COMPARISON OF TRANSFUSED VERSUS NON TRANSFUSED NOSOCOMIAL INFECTION OUTCOMES

Source: Taylor RW et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med 2006 July 34(9): 2302-2308

Reference

Zilberberg, M.D., et al. Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study. Critical Care, Vol 11:3, 6 June 2007.

Key Findings

Zillberberg et al. reported a strong independent relationship between packed red blood cell transfusion and the development of acute respiratory distress syndrome in the ICU (adjusted odds ratio of 2.80). They also identified an adjusted dose‐response relationship between increasing packed red blood cell units (PRBCs) transfused and increased risk of acute respiratory distress syndrome (ARDS). Receiving 1 to 2 units of PRBCs was associated with a greater than twofold increase in ARDS, 3 to 4 units with an almost threefold increase, and greater than 4 units with a greater than fivefold increase, compared with patients not exposed to any PRBC transfusions.

Details

Zilberberg et al. subsequently conducted a sub‐group analysis of the CRIT study to evaluate the association between packed red blood cell (PRBC) transfusion and acute respiratory distress syndrome (ARDS) in critically ill patients. The investigators focused on patients who did not have ARDS on admission, but developed ARDS during their ICU stay. After adjusting for multiple confounding factors, the authors reported a strong independent relationship between PRBC transfusion and the development of ARDS in the ICU (adjusted odds ratio of 2.80). Sighting reports estimating ARDS results in 3.6 million inpatient days of care annually and results from this study demonstrating that ARDS was associated with increased duration of ventilatory support, increased

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ICU and hospital length of stay and mortality, the authors suggest that their “findings should give physicians pause when considering transfusion” in at risk patients.

Reference

Amato, A., and Pescatori, M., Preoperative blood transfusions for the recurrence of colorectal cancer (Review). The Cochrane Collaboration, The Cochrane Library, 2009: Issue 4, p.1‐62

Key Findings

Amato A, and Pescatori M conducted a meta‐analysis which aimed to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This was accomplished by validating the results of a previously published meta‐analysis (Amato 1998); and by updating it to December 2004. Amato and Pescatori concluded that the updated meta‐analysis confirmed the previous findings. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seem necessary.

Details

The improvement of renal allograft survival by pre‐transplantation transfusions alerted the medical community to the potential detrimental effect of transfusions in patients being treated for cancer. Amato A, and Pescatori M, conducted a meta‐analysis which aimed to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This was accomplished by validating the results of a previously published meta‐analysis (Amato 1998); and by updating it to December 2004. Published papers were retrieved using Medline, EMBASE, the Cochrane Library, controlled trials web‐based registries, or the CCG Trial. The search strategy used was: {colon OR rectal OR colorectal} WITH {cancer OR tumour OR neoplasm} AND transfusion. The tendency not to publish negative trials was balanced by inspecting the proceedings of international congresses.

Patients undergoing curative resection of colorectal cancer (classified either as Dukes stages A‐C, Astler‐Coller stages A‐C2, or TNM stages T1‐3a/N0‐1/M0) were included if they had received any amount of blood products within one month of surgery. Excluded were patients with distant metastases at surgery, and studies with short follow‐up or with no data. A specific form was developed for data collection. Data extraction was cross‐checked, using the most recent publication in case of repetitive ones. Papers’ quality was ranked using the method by Evans and Pollock. Odds ratios (OR, with 95% confidence intervals) were computed for each study, and pooled estimates were generated by RevMan (version 4.2). When available, data were stratified for risk factors of cancer recurrence.

The findings of the 1998 meta‐analysis were confirmed, with small variations in some estimates. Updating it through December 2004 led to the identification of 237 references. Two‐hundred and one of them were excluded because they analysed survival (n=22), were repetitive (n=26), letters/reviews (n=66) or had no data (n=87). Thirty‐six studies on 12,127 patients were included: 23 showed a detrimental effect of PBT; 22 used also multivariable analyses, and 14 found PBT to be an independent prognostic factor. Pooled estimates of PBT effect on colorectal cancer recurrence yielded overall OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients in randomized controlled studies. Stratified meta‐analyses confirmed these findings, also when stratifying patients by site and stage of disease. The PBT effect was observed regardless of timing, type, and in a dose‐related fashion, although heterogeneity was detected. Data on surgical techniques was not available for further analysis.

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Amato and Pescatori concluded that the updated meta‐analysis confirmed the previous findings. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seem necessary.

Reference

DeFoe, G.R., et al., Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg, 2001. 71(3): p. 769‐76.

Key Findings

In a multi‐centre prospective observational study of 8004 consecutive patients undergoing isolated coronary artery bypass graft (CABG) surgery the Northern New England Cardiovascular Disease Study Group sought to address the question of whether the morbidity and mortality associated with haemodilution anaemia in CABG surgery with cardiopulmonary bypass is due to the anaemia or the red blood cell transfusions used to treat the anaemia. The authors conclude that haemodilution anaemia during cardiopulmonary bypass is associated with an increased risk of low‐output heart failure, however, management of that anaemia with red blood cell transfusion is independently associated with an increased risk of low‐output heart failure.

Details

In a multi‐centre prospective observational study of 8004 consecutive patients undergoing isolated coronary artery bypass graft (CABG) surgery the Northern New England Cardiovascular Disease Study Group sought to address the question of whether the morbidity and mortality associated with haemodilution anaemia in CABG surgery with cardiopulmonary bypass (as shown in an earlier study is due to the anaemia or the red blood cell transfusions used to treat the anaemia. The primary outcome measure in this study was low‐output heart failure (LOF). The authors explain that they used this measure because it is a good indicator of the outcome of intraoperative management. They also chose to analyse patients transfused with only 1 or 2 red blood cell units in order to minimise the confounding effect of more heavily transfused patients which may reflect management of active bleeding rather than routine anaemia. The investigators compared patients who received red blood cell transfusions (1 or 2 units) with patients receiving no red blood cell transfusions. They also analysed anaemia and outcome in nadir haematocrit (HCT) groups (HCT ≤20, 21 to 22, 23 to 24 and ≥25). In each nadir HCT group there were patients managed with and without red blood cell transfusions. Overall, both anaemia and red blood cell transfusion was associated with an increased risk of LOF. The risk of LOF was increased almost twofold in the transfused patients compared with those not transfused (12.4% vs. 6.8% respectively). After adjusting for all factors known to influence patient outcomes, both anaemia and red blood cell transfusion were still risk factors for LOF. Between each nadir HCT group there was a 10% increased risk of LOF. Red blood cell transfusion was associated with a 27% increased risk compared with no transfusion. The authors conclude that haemodilution anaemia during cardiopulmonary bypass is associated with an increased risk of LOF, however, management of that anaemia with red blood cell transfusion is independently associated with an increased risk of LOF.

Reference

Rogers, Mary A.M., et al. Hospital variation in transfusion and infection after cardiac surgery: a cohort study. BMC Medicine 2009, 7:37.

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Key Findings

Rogers, Mary A.M., et al. assessed hospital variation in blood use and outcomes in cardiac surgery patients. They concluded that allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system‐wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable indicating that quality efforts may be able to influence practice and improve outcomes.

Details

Rogers, Mary A.M., et al. assessed hospital variation in blood use and outcomes in cardiac surgery patients. They evaluated outcomes in 24,789 Medicare beneficiaries in the state of Michigan, USA, who received coronary artery bypass graft surgery from 2003 to 2006. Using a cohort design, patients were followed from hospital admission to assess transfusions, in‐hospital infection and mortality, as well as hospital readmission and mortality 30 days after discharge. Multilevel mixed‐effects logistic regression was used to calculate the intra‐hospital correlation coefficient (for 40 hospitals) and compare outcomes by transfusion status.

Overall, 30% (95 CI, 20% to 42%) of the variance in transfusion practices was attributable to hospital site. Allogeneic blood use by hospital ranged from 72.5% to 100% in women and 49.7% to 100% in men. Allogeneic, but not autologous, blood transfusion increased the odds of in‐hospital infection 2.0‐fold (95% CI 1.6 to 2.5), in‐hospital mortality 4.7‐fold (95% CI 2.4 to 9.2), 30‐day readmission 1.4‐fold (95% CI 1.2 to 1.6), and 30‐day mortality 2.9‐fold (95% CI 1.4 to 6.0) in elective surgeries. Allogeneic transfusion was associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, as well as infection with Clostridium difficile. For each 1% increase in hospital transfusion rates, there was a 0.13% increase in predicted infection rates. Rogers et al. concluded that allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system‐wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable indicating that quality efforts may be able to influence practice and improve outcomes.

Reference

Wu, W.C., et al., Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med, 2001. 345(17): p. 1230‐6.

Key Findings

Wu et al. assessed the benefit of transfusion in anaemic elderly patients with myocardial infarction by analysing a United States Medicare/Medicaid database of 234,769 patients. Univariate analysis demonstrated that transfusion was associated with decreased 30‐day mortality in patients admitted with a haemoglobin value ≤ 100 g/L, and a trend toward improved survival up to a haemoglobin value of 110 g/L. However, patients transfused with a haemoglobin value >110 g/L had an increased mortality. No multivariate or propensity score matching was performed and the <100 g/dL group had twice the number of do‐not‐resuscitate (DNR) orders, more diabetes and fewer aggressive cardiology and cardiac surgery interventions compared with the higher haemoglobin groups, resulting in considerable debate over the relevance of the findings of this study.

Details

To assess the benefit of transfusion in anaemic elderly patients with myocardial infarction (MI) Wu et al. analysed a United States Medicare/Medicaid database of 234,769 admitted over a one‐year period with a primary diagnoses of acute MI. After exclusions 78,769 patients 65 years of age or older were grouped into different haematocrit/haemoglobin groups for evaluation. 50% of the

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evaluation group were anaemic (defined as a haemoglobin value less than 13 g/L). 4.7% of the entire evaluable group received a blood transfusion. Univariate analysis demonstrated that transfusion was associated with decreased 30‐day mortality in patients admitted with a haemoglobin value ≤ 100 g/L, and a trend toward improved survival up to a haemoglobin value of 110 g/L. However, patients transfused with a haemoglobin value >110 g/L had an increased mortality. No multivariate or propensity score matching was performed and the <100 g/dL group had twice the number of do‐not‐resuscitate (DNR) orders, more diabetes and fewer aggressive cardiology and cardiac surgery interventions compared with the higher haemoglobin groups, resulting in considerable debate over the relevance of the findings of this study.

Reference

Rao, S.V., et al., Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA, 2004. 292(13): p. 1555‐62.

Key Findings

A study subsequent to Wu (see above) of patients with myocardial infarction came to a different conclusion. Rao et al. analysed data from three large international randomised controlled trials involving 24,111 patients with acute coronary syndrome. After multivariate and propensity analysis, adjusting for timing of events, bleeding, type of infarction, nadir haemoglobin and procedure, blood transfusion was associated with a 3.94 times increased risk for 30‐day mortality. When examined by haemoglobin levels, the investigators found an association between transfusion and increased 30‐day mortality at a mean haemoglobin > 83 g/L. The adjusted increased hazard (odds ratio) for death was 168.64 for a mean haemoglobin level of 100 g/L and 291.64 for mean nadir haemoglobin of 117 g/L. They found no association between transfusion and increased mortality and, conversely, no benefit, in patients with a mean haemoglobin < 83 g/L.

Details

A study subsequent to Wu (see above) of patients with MI came to a different conclusion. Rao et al. analysed data from three large international randomised controlled trials involving 24,111 patients with acute coronary syndrome. Whereas Wu et al. excluded patients younger than 65 years, those with bleeding within 48 hours of admission, and those who underwent cardiac surgery, Rao et al. included all patients, regardless of age, bleeding events, or interventions. Ten per cent of patients underwent at least one blood transfusion. The investigators found that patients who underwent transfusion had a significantly higher unadjusted rate of 30‐day death (8.00% vs. 3.08%; P<.001), myocardial infarction (MI) (25.16% vs. 8.16%; P<.001), and combined death/MI (29.24% vs. 10.02%; P<.001) compared with patients who did not undergo transfusion. After multivariate and propensity analysis, adjusting for timing of events, bleeding, type of infarction, nadir haemoglobin and procedure, blood transfusion was associated with a 3.94 times increased risk for 30‐day mortality. When examined by haemoglobin levels, the investigators found an association between transfusion and increased 30‐day mortality at a mean haemoglobin > 83 g/L. The adjusted increased hazard (odds ratio) for death was 168.64 for a mean haemoglobin level of 100 g/L and 291.64 for mean nadir haemoglobin of 117 g/L. They found no association between transfusion and increased mortality and, conversely, no benefit, in patients with a mean haemoglobin < 83 g/L.

Reference

Croce, M.A., et al., Transfusions result in pulmonary morbidity and death after a moderate degree of injury. J Trauma, 2005. 59(1): p. 19‐23; discussion 23‐4.

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Key Findings

In an effort to minimise the confounding contribution of injury and shock to outcome, Croce et al. evaluated the association between delayed transfusion and serious respiratory complications in a cohort of ICU patients with less severe blunt trauma who received no transfusion within the initial 48 hours after admission. They found blood transfusion was still an independent predictor of serious adverse outcome. The authors concluded, “This study demonstrates that transfusions are not innocuous and that aggressive pursuit of transfusion substitutes is warranted.”

Details

In an effort to minimise the confounding contribution of injury and shock to outcome, Croce et al. evaluated the association between delayed transfusion and serious respiratory complications (ventilator‐associated pneumonia [VAP], acute respiratory distress syndrome [ARDS]) and death) in a cohort of ICU patients with less severe (ISS <25) blunt trauma who received no transfusion within the initial 48 hours after admission. Of the 5,260 patients who met study criteria, 778 (15%) received delayed transfusion. Logistic regression analysis identified delayed transfusion as being independently associated with VAP, ARDS and death. In a subgroup analysis of younger patients (age <50), with even less injury (ISS <16, Glasgow Comma Score [GCS] >11, chest Abbreviated Injury Scale [AIS] <3), and minimal shock (base excess ≥ 5.0 mEq/L), blood transfusion was still an independent predictor of serious adverse outcome. The authors concluded, “This study demonstrates that transfusions are not innocuous and that aggressive pursuit of transfusion substitutes is warranted.”

Reference

Dunne, J.R., et al., Allogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. Surg Infect (Larchmt), 2004. 5(4): p. 395‐404.

Key Findings

Dunne et al. in a study of 9539 trauma patients found that blood transfusion within the first 24 hours was an independent predictor of systemic inflammatory response syndrome (SIRS) as well as mortality, ICU admission, and ICU length of stay. Patients who received blood transfusion in the first 24 hours after trauma had a significantly increased risk of SIRS compared to those not transfused.

Details

Dunne et al. in a study of 9539 trauma patients found that blood transfusion within the first 24 hours was an independent predictor of systemic inflammatory response syndrome (SIRS) as well as mortality, ICU admission, and ICU LOS. Patients who received blood transfusion in the first 24 hours after trauma had a significantly increased risk of SIRS (relative risk ratios 2.1 to 5.4 for SIRS scores 1–4) compared to those not transfused. Multinomial logistic regression analysis revealed that after controlling for age, ISS, GCS, gender, and race blood transfusion was an independent predictor of SIRS, (OR 2.43, 95% CI 1.99–2.95; p <0.0001). Transfused patients had significantly increased mortality rates (22.2% vs. 1.4%, p <0.0001), increased ICU admission rates (57.4% vs. 7.4%; p <0.0001), and increased ICU LOS (16.8 vs. 9.9, p < 0.00001) compared to non‐transfused patients. Transfused patients also had significantly increased hospital LOS (14.5 vs. 2.555 days, p <0.00001) compared to non‐transfused patients. After controlling for other factors that affect trauma outcome, including age, ISS, GCS, race, and gender, transfused patients had a fourfold increased risk of mortality (OR 4.23, 95% CI 3.07–5.84, p <0.0001) and a greater than fourfold increased risk of ICU admission (OR 4.62, 95% CI 3.84–5.55, p <0.0001) compared to non‐transfused patients. In addition, linear regression analysis revealed blood transfusion to be an independent risk factor for ICU LOS

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(5.2 days longer ICU LOS for the transfused group; p <0.0001) and hospital LOS (7.3 days longer hospital LOS for the transfused group; p <0.0001).

Reference

Rogers, M.A., et al., Allogeneic blood transfusions explain increased mortality in women after coronary artery bypass graft surgery. Am Heart J, 2006. 152(6): p. 1028‐34.

Key Findings

Given the greater postoperative mortality rate in women compared to men following coronary artery bypass graft (CABG) surgery, Rogers and colleagues investigated whether the higher transfusion rate in women may contribute to the gender‐different mortality. They found women were 3.4 times more likely to be transfused than men and received a significantly greater number of units. Women were 1.5 times more likely to die within 100 days of surgery than men. However, when adjusted for blood transfusion, there was no longer a significant difference in the mortality between men and women – suggesting blood transfusion being a risk factor for mortality. The authors conclude that this study suggests the increased mortality in women following CABG surgery is likely due to their increased receipt of blood transfusion.

Details

Given the greater postoperative mortality rate in women compared to men following coronary artery bypass graft (CABG) surgery, Rogers and colleagues investigated whether the higher transfusion rate in women may contribute to the gender‐different mortality. Of the 9,218 patients included in the study 74.8% received an allogeneic blood transfusion. This study confirmed that women are more likely to be transfused than men (88.2% vs. 66.7%). After adjusting for variables (age, race, 30 co morbidities and urgency of admission) women were 3.4 times more likely to be transfused than men and received a significantly greater number of units. Patients who received blood had a significantly increased infection rate compared with those not receiving blood (14.6% vs. 4.9%). The infection rate in patients receiving autologous blood only (n=90) was 5.6%. Compared with non‐transfused, the risk of transfused patients developing a specific site infection increased 6.8 times for septicaemia, 3.5 times for respiratory tract, 2.3 times for urinary tract, 2.4 times for digestive tract, 3.6 times for heart and 3.7 times for device‐related. The authors also found a dose‐dependent relationship, with the infection rate increasing with the number of units transfused (1‐4 U = 13.6%, 5‐9 U = 25.3%, 50‐99 U = 30.8%). The 100‐day mortality rate was 9.4% for transfused patients compared with 1.5% in those not transfused. After adjusting for variables, transfused patients were 5.6 times more likely to die within 100 days of surgery compared with those not transfused. Women were 1.5 times more likely to die within 100 days of surgery than men. However, when adjusted for blood transfusion, there was no longer a significant difference in the mortality between men and women – suggesting blood transfusion being a risk factor for mortality. The authors conclude that this study suggests the increased mortality in women following CABG surgery is likely due to their increased receipt of blood transfusion.

Reference

Murphy, G.J., et al. Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery. Circulation. 2007;116:2544‐2552.

Key Findings

Murphy, G.J., et al. aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. They concluded that red blood cell transfusion in patients having

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cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.

Details

Murphy, G.J., et al. aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. They concluded that red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs. Clinical, haematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicaemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were pre‐specified as co‐primary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modelling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus non‐transfused patients were 3.38 (95% confidence interval [CI], 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times [95% CI, 1.37 to 1.46], varying from 1.11 for 1 U to 3.35 for _9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio [HR], 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; _1 year: HR, 1.32; 95% CI, 1.08 to 1.64).

Reference

Lacroix J, Hebert PC, James S, et al., for the TRIPICU Investigators, the Canadian Critical Care Trials Group, and the Pediatric Acute Lung Injury and Sepsis Investigators Network. N Eng J Med 2007; 356 (16):1609‐1619

Key Findings

Dr Jacque Lacroix and colleagues report on their 2007 international multicenter Transfusion Requirements in the Pediatric Intensive Care Unit (TRIPICU) Study, a trial, described by the authors of the accompanying editorial, as having implications for understanding the role of such transfusions in all critically ill patients. The investigators compared a liberal versus a restrictive transfusion threshold in stable critically ill children. Results showed that the restrictive transfusion threshold resulted in a 44% reduction in the number of red blood cell transfusions and a 96% reduction in the number of patients exposed to any transfusion when compared with the liberal threshold. This was achieved without any increase in measured adverse outcomes. The authors conclude that a restrictive transfusion threshold in stable critically ill children in ICU can be used safely to reduce transfusion exposure. They caution, however, on applying this finding to other patient groups. After commenting on this trial and reviewing the results of three other randomized trials evaluating transfusion triggers, Drs Howard Corwin and Jeffery Carson in their editorial conclude that the overall evidence does not support liberal use of transfusion in critically ill patients. They state, “Red‐cell transfusion should no longer be regarded as ‘may help, will not hurt’ but, rather, should be approached as ‘first do no harm.”

Details

Dr Jacque Lacroix and colleagues report on their 2007 international multicenter Transfusion Requirements in the Pediatric Intensive Care Unit (TRIPICU) Study, a trial, described by the authors of the accompanying editorial, as having implications for understanding the role of such transfusions

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in all critically ill patients. The investigators compared a liberal versus a restrictive transfusion threshold in stable critically ill children. Six hundred and thirty seven eligible patients between the ages of 3 days and 14 years were randomized to one of the two groups: 317 to the liberal transfusion threshold group (haemoglobin level of 9.5 g/dL) and 327 to the restrictive transfusion threshold group (haemoglobin level of 7 g/dL). They compared the two groups with regard to both the total number of transfusions per patient and the proportion of patients who avoided transfusions. All blood used in the study was pre‐storage leukocyte‐reduced. The primary outcome measure was a composite of death and multiple‐organ‐dysfunction syndrome. Secondary outcomes included sepsis, infections, transfusion reactions, adverse events and intensive care unit (ICU) and hospital length of stay. Results showed that the restrictive transfusion threshold resulted in a 44% reduction in the number of red blood cell transfusions and a 96% reduction in the number of patients exposed to any transfusion when compared with the liberal threshold. This, the authors report, was achieved without any increase in measured adverse outcomes. Both primary and secondary outcome measures were not significantly different between groups. The authors note that this result, in relation to adverse outcomes, differs from the only large randomized controlled trial comparing a liberal versus a restrictive transfusion strategy in critically ill adult patients, a study in which organ failure, other complications and in‐hospital mortality were significantly higher in the liberal group compared with the restrictive group. The authors present possible factors contributing to the different outcome findings. The authors conclude that a restrictive transfusion threshold in stable critically ill children in ICU can be used safely to reduce transfusion exposure. They caution, however, on applying this finding to other patient groups. After commenting on this trial and reviewing the results of three other randomized trials evaluating transfusion triggers, Drs Howard Corwin and Jeffery Carson in their editorial conclude that the overall evidence does not support liberal use of transfusion in critically ill patients. They state, “Red‐cell transfusion should no longer be regarded as ‘may help, will not hurt’ but, rather, should be approached as ‘first do no harm.”

Reference

Hajjar, Ludhmila A., et al. Transfusion Requirements After Cardiac Surgery: The TRACS Randomized Controlled Trial. JAMA, 2010;304(14):1559‐1567.

Key Findings

The objective of the 2010 Transfusion Requirements After Cardiac Surgery (TRACS) study by Hajjar, Ludhmila A., et al. was to define whether a restrictive perioperative red blood cell transfusion strategy was as safe as a liberal strategy in patients undergoing elective cardiac surgery. The study found that, Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days. The authors concluded that, among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in non‐inferior rates of the combined outcome of 30‐day all‐cause mortality and severe morbidity.

Details

The objective of the 2010 Transfusion Requirements After Cardiac Surgery (TRACS) study by Hajjar, Ludhmila A., et al. was to define whether a restrictive perioperative red blood cell transfusion strategy was as safe as a liberal strategy in patients undergoing elective cardiac surgery. The TRACS study, a prospective, randomized, controlled clinical non‐inferiority trial was conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral centre in Brazil. Consecutive adult patients (n=502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention‐to‐treat. Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit_30%) or to a restrictive strategy (hematocrit_24%). Composite end point of 30‐day all‐cause mortality and severe morbidity

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(cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The non‐inferiority margin was predefined at −8% (i.e., 8% minimal clinically important increase in occurrence of the composite end point). Haemoglobin concentrations were maintained at a mean of 10.5 g/dL(95%confidence interval [CI], 10.4‐10.6) in the liberal‐strategy group and 9.1 g/dL (95% CI, 9.0‐9.2) in the restrictive‐strategy group (P_.001). A total of 198 of 253 patients (78%) in the liberal‐strategy group and 118 of 249 (47%) in the restrictive‐strategy group received a blood transfusion (P_.001). Occurrence of the primary end point was similar between groups (10% liberal vs11%restrictive; between‐group difference,1%[95% CI,−6%to 4%]; P=.85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1‐1.4]; P=.002). Hajjar, Ludhmila A., et al. concluded that, among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in non‐inferior rates of the combined outcome of 30‐day all‐cause mortality and severe morbidity.

Reference

Jeschke, M.G., et al., Blood transfusions are associated with increased risk for development of sepsis in severely burned pediatric patients. Crit Care Med, 2007. 35(2): p. 579‐83.

Key Findings

Jeschke and colleagues investigated the association between allogeneic blood transfusion and infection and mortality in severely burned paediatric patients. Even after adjusting for the known effects of increased total body surface area burn and inhalation injury on sepsis, the authors conclude that receiving >20 units of red blood cells significantly increased the risk of sepsis. Of interest the investigators included weight as a covariate and report that it appears that the total amount of red blood cells transfused determined the risk, not the relative amount, that is, red blood cells given per kilogram.

Details

Jeschke and colleagues investigated the association between allogeneic blood transfusion and infection and mortality in severely burned paediatric patients. Their retrospective cohort study included 277 patients admitted to their institution from 1997 to 2004 with a burn >30% total body surface area (TBSA). The study’s design attempted to include only transfusions that were given before patients became clinically infected or septic. Patients were stratified into groups by small, medium and large TBSA burns (<40%, 40‐60% and >60% respectively) and whether or not they had inhalation injury. Groups were further divided according to whether they received “low” or “high” amounts of blood products and by the number of operations. Results showed that there was no significant increase in sepsis in patients with small burns given either low or high amounts of blood. In patients with large burns the risk of developing infection increased from 8% in the low red blood cell transfusion group (<20 units) to 58% in the high red blood cell group (>20 units). In large burn patients the mortality rate was 6% when receiving low amounts of blood and 30% when receiving high amounts (odds ration [OR] = 6.79). In the large burn group with inhalation injury the mortality rate was 11% in the low red blood cell group and 72% in the high red blood cell group (OR=11.6). Even after adjusting for the known effects of increased TBSA burn and inhalation injury on sepsis, the authors conclude that receiving >20 units of red blood cells significantly increased the risk of sepsis. Of interest the investigators included weight as a covariate and report that it appears that the total amount of red blood cells transfused determined the risk, not the relative amount, that is, red blood cells given per kilogram.

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Reference

Marik, PE., et al., Effect of Stored‐Blood Transfusion on Oxygen Delivery in Patients with Sepsis. JAMA. 1993;269(23):3024‐3029.

Key Findings

Marik et al. conducted a prospective, controlled, interventional study in 1993 to determine the effect of red blood cell transfusion on gastrointestinal and whole‐body oxygen uptake in a multidisciplinary intensive care unit of a tertiary care teaching hospital. They concluded that they had failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. They postulated that the poorly deformable transfused red blood cells cause microcirculatory occlusion in some organs, which may lead to tissue ischemia in some organs.

Details

Marik et al. conducted a prospective, controlled, interventional study in 1993 to determine the effect of red blood cell transfusion on gastrointestinal and whole‐body oxygen uptake in a multidisciplinary intensive care unit of a tertiary care teaching hospital. Twenty‐three critically ill patients with sepsis undergoing mechanical ventilation were the subjects of the study. Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method. Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability. Measurements were made prior to transfusion of 3 U of packed red blood cells. These measurements were then repeated immediately following transfusion, as well as 3 and 6 hours later. There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours post‐transfusion (including those patients with an elevated arterial lactate concentration). However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients. More importantly, they found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r=‐.71; P<.001). In those patients receiving blood that had been stored for more than 15 days, the gastric intramucosal pH consistently decreased following the red blood cell transfusion.

Twenty‐three critically ill patients with sepsis undergoing mechanical ventilation were the subjects of the study. Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method. Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability. Measurements were made prior to transfusion of 3 U of packed red blood cells. These measurements were then repeated immediately following transfusion, as well as 3 and 6 hours later. There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours post‐transfusion (including those patients with an elevated arterial lactate concentration). However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients. More importantly, they found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r=‐.71; P<.001). In those patients receiving blood that had been stored for more than 15 days, the gastric intramucosal pH consistently decreased following the red blood cell transfusion.

Marik et al. concluded that they had failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. They postulated that the poorly deformable transfused red blood cells cause microcirculatory occlusion in some organs, which may lead to tissue ischemia in some organs.

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Reference

Koch, C.D., et al. Duration of Red‐Cell Storage and Complications after Cardiac Surgery. N Engl J Med 358:12, March 20, 2008, p.1229‐39.

Key Findings

Stored red cells undergo progressive structural and functional changes over time. Koch, C.D., et al. tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells are stored for more than two weeks. They concluded that, in patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than two weeks was associated with a significantly increased risk of postoperative complications as well as reduced short‐term and long‐term survival.

Details

Stored red cells undergo progressive structural and functional changes over time. Koch, C.D., et al. tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells are stored for more than two weeks. They examined data from patients given red‐cell transfusions during coronary‐artery bypass grafting, heart‐valve surgery, or both between June 30, 1998, and January 30, 2006. A total of 2872 patients received 8802 units of blood that had been stored for 14 days or less (“newer blood”), and 3130 patients received 10,782 units of blood that had been stored for more than 14 days (“older blood”). Multivariable logistic regression with propensity‐score methods was used to examine the effect of the duration of storage on outcomes. Survival was estimated by the Kaplan–Meier method and Blackstone’s decomposition method. The median duration of storage was 11 days for newer blood and 20 days for older blood. Patients who were given older units had higher rates of in‐hospital mortality (2.8% vs. 1.7%, P = 0.004), intubation beyond 72 hours (9.7% vs. 5.6%, P<0.001), renal failure (2.7% vs. 1.6%, P = 0.003), and sepsis or septicaemia (4.0% vs. 2.8%, P = 0.01). A composite of complications was more common in patients given older blood (25.9% vs. 22.4%, P = 0.001). Similarly, older blood was associated with an increase in the risk‐adjusted rate of the composite outcome (P = 0.03). At 1 year, mortality was significantly less in patients given newer blood (7.4% vs. 11.0%, P<0.001).

Koch, C.D., et al. concluded that, in patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than two weeks was associated with a significantly increased risk of postoperative complications as well as reduced short‐term and long‐term survival.

Reference

Tsai, A.G., et al. Perfusion vs. oxygen delivery in transfusion with ‘‘fresh” and ‘‘old” red blood cells: The experimental evidence. Transfusion and Apheresis Science 43 (2010), p.69–78.

Key Findings

Tsai, A.G., et al. reviewed the experimental evidence showing systemic and microvascular effects of blood transfusions instituted to support the organism in extreme haemodilution and haemorrhagic shock, focusing on the use of fresh vs. stored blood as a variable. The question: ‘‘What does a blood transfusion remedy?” was analysed in experimental models addressing systemic and microvascular effects showing that oxygen delivery is not the only function that must be addressed. They concluded that that fresh blood is intrinsically a better resuscitation fluid than older, stored blood in the animal model systems in which it has been carefully studied.

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Details

Tsai, A.G., et al. reviewed the experimental evidence showing systemic and microvascular effects of blood transfusions instituted to support the organism in extreme haemodilution and haemorrhagic shock, focusing on the use of fresh vs. stored blood as a variable. The question: ‘‘What does a blood transfusion remedy?” was analysed in experimental models addressing systemic and microvascular effects showing that oxygen delivery is not the only function that must be addressed. In extreme haemodilution and haemorrhagic shock blood transfusions simultaneously restore blood viscosity and oxygen carrying capacity, the former being critically needed for re‐establishing a functional mechanical environment of the microcirculation, necessary for obtaining adequate capillary blood perfusion. Increased oxygen affinity due to DPG depletion is shown to have either no effect or a positive oxygenation effect, when the transfused red blood cells (RBCs) do not cause additional flow impairment due to structural malfunctions including increased rigidity and release of haemoglobin. Tsai, A.G., et al. conclude that that fresh blood is intrinsically a better resuscitation fluid than older, stored blood in the animal model systems in which it has been carefully studied. It is also apparent that blood transfusions are called for to restore oxygen carrying capacity, while one of the major problems is deficient microvascular perfusion and function. In fact it is questionable whether a blood transfusion is the optimal remedy for re‐establishing tissue perfusion in an organism subjected to haemodilution and haemorrhage, or both. A precise understanding of the mechanisms involved in blood transfusion may be intrinsically impossible, because blood composition per se is a moving target. Distinguishing between ‘‘fresh” and ‘‘old” RBCs overlooks that the distribution of RBC age in the circulation is presumed to be approximately Gaussian, with an average centred at their circulatory half‐life, therefore even ‘‘fresh” blood has a fraction of RBCs at the end of their cycle. Experimental studies in transfusion studies have presently addressed the question and provide preliminary answer to: What is the problem that must be remedied when a blood transfusion is called for? We propose that oxygen is only one part of the problem, and that microscopic perfusion is the other component. Remarkably their relative importance is not yet established, however there is evidence that adequate restoration of microvascular perfusion deficiency in anaemia and haemorrhagic resuscitation may be as efficacious as restoring oxygen carrying capacity, therefore potentially significantly reducing the use of blood. Although experimental studies seldom reproduce emergency and clinical conditions, nonetheless they serve to explore fundamental physiological mechanisms in the microcirculation that cannot be directly studied in humans.

Reference

Stephen Kenneth O'Mara, BSc. MBBS, FRACP, FRCPA, John Ferguson, MBBS, FRACP, FRCPA and Michael Manolis, Assoc.Dip.HealthScience, Tech.Cert.Path. Poster 346 Blood Transfusion Increases Hospital Acquired Septicaemia. 52nd ASH Annual Meeting and Exposition, December 4‐7, 2010, Orange County Convention Center, Orlando, FL.

Key Findings

An abstract entitled Blood Transfusion Increases Hospital Acquired Septicaemia by O'Mara et al., from the Hunter New England Health Service, Australia was presented at the 52nd ASH Annual Meeting and Exposition, December 4‐7, 2010, Orlando, Florida. The abstract said the study showed there was a statistically significant increase in septicaemia following red cell transfusion. The null hypothesis was rejected. The data base was examined by the age of red cells transfused and its effect on nosocomial septicaemia. There was a statistically significant effect of older blood on the rate of septicaemia.

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Details

FIGURE 105: POSTER FROM 52ND ASH ANNUAL MEETING AND EXPOSITION, FLORIDA

52ND ASH ANNUAL MEETING AND EXPOSITION, DECEMBER 4‐7, 2010,

Orange County Convention Center, Orlando, Florida

346 Blood Transfusion Increases Hospital Acquired Septicaemia

Poster Session: Basic Science and Clinical Practice in Blood Transfusion: Poster II

Monday, December 6, 2010, 6:00 PM‐8:00 PM

Hall A3/A4 (Orange County Convention Center), Poster Board III‐125

Stephen Kenneth O'Mara, BSc., MBBS, FRACP, FRCPA1, John Ferguson, MBBS, FRACP, FRCPA2 and Michael Manolis, Assoc.Dip.HealthScience, Tech.Cert.Path3

1Haematology and Clinical Governance, Hunter New England Health, Tamworth, Australia

2Infectious diseases, Hunter Area Pathology service, Newcastle, Australia

3Transfusion Laboratory, Hunter Area Pathology service, Newcastle

The rate of septicaemia was measured following blood transfusion in patients admitted to hospital greater than 48 hours. The data was collected prospectively and analysed retrospectively. The aim of the analysis was to disprove that red cell transfusion increased the rate of hospital acquired septicaemia. Data was extracted on patients who had a transfusion and an episode of septicaemia between 1999 and 2008 at a university teaching hospital, John Hunter Hospital, Newcastle, Australia (JHH). The database contained information on 20161 transfusion events of 102,600 units of packed red cells. The septicaemia database contained 8375 patients with blood culture proven septicaemia.

Blood was issued using a computerised cross matching system. Analysis of the issuing of blood found no bias in the age of blood issued based on age, sex, number of units or by year of issue. All patients having a septicaemic event recorded following transfusion were analysed and compared to septicaemia occurring in all admissions greater than 48hrs in which no transfusion occurred. All patients who were diagnosed with septicaemia in the 6 months prior to transfusion were excluded as were patients who received five or more units of packed red cells to exclude the bias from the sickest patients. All patients whose septicaemia occurred greater than 16 days after transfusion were excluded as were patients whose septicaemia occurred before the second day after transfusion. A total of 258 patients were reviewed to test the hypothesis (Table 1).

There was a statistically significant increase in septicaemia following red cell transfusion. The null hypothesis was rejected. The data base was examined by the age of red cells transfused and its effect on nosocomial septicaemia. There was a statistically significant effect of older blood on the rate of septicaemia. Packed red cells transfused less than 14 days of age had no effect on the septicaemia rate. Blood that was 14‐28 days of age increased the rate of nosocomial septicaemia by 1.65. Red Cells that were between 29 and 35 days of age increased the rate of septicaemia by 2.5 times. Blood that was between 36 and 42 days of age increased the rate by approximately 4.4 times, with the absolute risk of developing septicaemia within 15 days being approximately 4% (Table 2). The time course of septicaemia was examined for patients receiving at least one unit of 28 day old blood. It was

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found that the risk of sepsis lasted less than 15 days p<0.001. The conclusion of our analysis suggests that packed red cells older than 14 days increase the risk of septicaemia in hospitalised patients, this effect continues to rise until 42 days post collection.

Table 1

N Odds Ratio(CI)

Total cases of nosocomial septicaemia

1684

Admissions greater than 48 hours 175,325

Prior to exclusions

All transfusions

No previous sepsis

790 10.2

(10.1‐10.3)

Study Group

Less than 5 units Transfusion.

No previous sepsis.

Septicaemia >2 days <16days

258 2.02

(1.92‐2.12)

Table 2

Age of oldest red cell pack

Less than 15 days of age

15 to 28 days of age

29‐35 days of age 36‐42 days of age

Percentage

transfused

24% 49% 14% 12%

Number of transfusions < 5 units

3524 7161 2115 1802

Septicaemia observed

33 102 52 71

Odds ratio 0.98 1.54 2.55 4.4

Confidence Interval.

0.65‐1.31 1.34‐1.74 2.26‐2.84 4.16‐4.64

Disclosures: No relevant conflicts of interest to declare

Source: Stephen Kenneth O'Mara, BSc. MBBS, FRACP, FRCPA, John Ferguson, MBBS, FRACP, FRCPA and Michael Manolis, Assoc.Dip.HealthScience, Tech.Cert.Path. Poster 346 Blood

P a g e | 262

Transfusion Increases Hospital Acquired Septicaemia. 52nd ASH Annual Meeting and Exposition, December 4-7, 2010, Orange County Convention Center, Orlando, FL

References

The SAFE Study Investigators, A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit. N Engl J Med, 27 May 2004, 350;22, 2247‐2256.

Simon R Finfer, Neil W Boyce and Robyn N Norton, The SAFE Study: a landmark trial of the safety of albumin in intensive care. MJA Volume 181, Number 5, 6 September 2004.

The SAFE Study Investigators 2007, ‘Saline or albumin for fluid resuscitation in patients with traumatic brain injury.’ New England Journal of Medicine; 357(9): 874‐84.

Key Findings

The Saline versus Albumin Fluid Evaluation (SAFE) study which was published in May 2004 looked at the use of albumin. The SAFE Investigators issued a subsequent report in 2007 of a post hoc follow‐up study of patients with traumatic brain injury who were enrolled in the SAFE study. The study was a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian Red Cross Blood Service, and The George Institute for International Health. The SAFE Investigators concluded that, in patients in the ICU, use of either 4% albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

Following the conduct of a post hoc follow‐up study in 2007 of patients with traumatic brain injury who were enrolled in the study, they concluded that fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline.

Details

The Saline versus Albumin Fluid Evaluation (SAFE) study which was published in May 2004 looked at the use of albumin. The SAFE Investigators issued a subsequent report in 2007 of a post hoc follow‐up study of patients with traumatic brain injury who were enrolled in the SAFE study.

The SAFE Study was a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian Red Cross Blood Service, and The George Institute for International Health. The SAFE Investigators concluded that, in patients in the ICU, use of either 4% albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

The study which was published in May 2004 noted that, “It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival”. They conducted a multicentre, randomized, double‐blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. The SAFE Investigators randomly assigned patients who had been admitted to the ICU to receive either 4% albumin or normal saline for intravascular‐fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28‐day period after randomization.

Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 per cent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single‐organ and multiple‐organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (±SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in the saline group, P=0.44), days spent in the hospital (15.3±9.6 and

P a g e | 263

15.6±9.6, respectively; P=0.30), days of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively; P=0.74), or days of renal‐replacement therapy (0.5±2.3 and 0.4±2.0, respectively; P=0.41).

The study identified six predefined subgroups: patients with and without trauma, with and without severe sepsis, and with and without acute respiratory distress syndrome (ARDS). As a previous meta‐analysis had suggested that trauma patients resuscitated with colloid solutions had higher mortality than those resuscitated with crystalloid solutions, trauma was a stratification variable in the study. Patients with severe sepsis and ARDS were identified at baseline to determine whether the increased capillary permeability to albumin seen in those conditions resulted in a treatment effect that differed from that seen in the study patients without those conditions. Within the predefined subgroups there was limited evidence of a treatment effect favouring saline in patients with trauma, and favouring albumin in patients with severe sepsis. The possibly detrimental effect of albumin in patients with trauma was limited to patients with evidence of traumatic brain injury, namely those patients admitted to the ICU as a result of trauma who had a documented, unsedated Glasgow Coma Scale score less than 14 and evidence of brain injury on cerebral computed tomography.

The investigators cautioned that such subgroup differences frequently occur by chance, and the accompanying editorial advised cautious interpretation of the subgroup findings. Thus, the study demonstrated that, in this heterogeneous population of adult ICU patients, albumin can be considered safe, without demonstrating any clear efficacy advantage over saline.

The SAFE Investigators subsequent report in 2007 noted that the Saline versus Albumin Fluid Evaluation study suggested that patients with traumatic brain injury resuscitated with albumin had a higher mortality rate than those resuscitated with saline. Following the conduct of a post hoc follow‐up study of patients with traumatic brain injury who were enrolled in the study, they concluded that fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline.

A P P E ND I X 6

Further Information on Data Sets Related to BloodNet Proposal

Fresh Clotting Factors IVIg All Other Products / services

Donor management

eProgesa (Supplier)

--- --- ---

Quality

eProgesa (Supplier)

Supplier Systems

Supplier Inventory

ORBS

Supplier Wastage

IDMS

Orders by AHP

ORBS ABDR NIMS ORBS

Authorisation

--- ABDR NIMS ---

Inventory of and Receipt by AHP

ORBS

Fate of Product (DRG / Wastage)

ORBS ABDR ORBS ORBS

Outcome (identifiers for linkage)

ORBS

Outcome (outcome captured)

--- ABDR NIMS ---

Reporting (operational & performance)

BIG RED

Supplier payments IDMS

Contract performance IDMS

Jurisdictional payments IDMS Supply plan performance IDMS End user interface

blood.gov.au and 13 000 BLOOD (for support)

SOURCE: NATIONAL BLOOD AUTHORITY, 2011

A P P E ND I X 7

Price Assumptions for Blood Demand Model

PRICE INCREASES

PRODUCT DESCRIPTION 2010‐11 2011‐12 2012‐13 2013‐14 2014‐15 2015‐16 Onwards

ARCBS PRODUCTS Unit

Red Cell Products

WB Red Cell – Leucodepleted >200mL or equivalent

4.9% ‐1.0% 4.1% 4.1% 4.1% 4.1%

WB Paediatric Red Cell ‐ Leucodepleted (Set of 4) 25‐100mL ‐6.5% ‐24.4% 4.1% 4.1% 4.1% 4.1%

WB Washed Red Cell ‐ Leucodepleted >130mL or equivalent

‐22.5% ‐25.7% 4.1% 4.1% 4.1% 4.1%

Apheresis Red Cell ‐ Leucodepleted >240ml ‐22.5% ‐100.0%

Platelet Products

WB Platelet Pool – Leucodepleted >160mL or equivalent

6.78% 7.27% 4.10% 4.10% 4.10% 4.10%

Apheresis Platelet – Leucodepleted 100‐400mL 0.02% ‐11.32% 4.10% 4.10% 4.10% 4.10%

Paediatric Apherisis Platelet ‐ Leucodepleted (Set of 4)

40‐60mL ‐8.77% ‐54.39% 4.10% 4.10% 4.10% 4.10%

Clinical Fresh Frozen Plasma Products

WB Clinical FFP ‐ Buffy Coat Poor 295mL +/‐10% 172.53% 73.54% 4.10% 4.10% 4.10% 4.10%

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PRICE INCREASES


Paediatric WB Clinical FFP (Set of 4) 74mL +/‐10% 65.89% ‐65.81% 4.09% 4.10% 4.10% 4.10%

Apherisis Clinical FFP 295mL+/‐10% 493.29% ‐11.60% 4.10% 4.10% 4.10% 4.10%

Cryoprecipitate Products

WB Cryoprecipitate 30‐40mL 141.02% ‐76.93% 4.10% 4.11% 4.09% 4.09%

Apheresis Cryoprecipitate 60mL +/‐ 10% 68.52% ‐47.05% 4.10% 4.10% 4.10% 4.10%

Cryo‐depleted Plasma Products

WB Cryo‐depleted Plasma >165mL 144.47% ‐76.66% 4.10% 4.09% 4.10% 4.10%

Apherisis Cryo‐depleted Plasma >500mL 68.75% ‐50.70% 4.10% 4.10% 4.10% 4.10%

Other Products

Autologous Donation N/A 47.52% 394.06% 4.10% 4.10% 4.10% 4.10%

Directed donation complying with AHMAC Guidelines

N/A 51.47% 355.83% 4.10% 4.10% 4.10% 4.10%

Therapeutic Venesections for WB for Discard N/A ‐ Collection discarded

4.84% 37.98% 4.10% 4.10% 4.10% 4.10%

Serum Eye Drops Single collection unit

‐2.25% ‐19.27% 4.10% 4.10% 4.10% 4.10%

Granulocytes TBD 0.00% 0.00% 4.10% 4.10% 4.10% 4.10%

Plasma for fractionation kg ‐16.42% 17.91% 4.10% 4.10% 4.10% 4.10%

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PRICE INCREASES


CSL PRODUCTS

Albumin Group

Albumex® 20 ‐ 10ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Albumex® 20 ‐ 100ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Albumex® 4 ‐ 50ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Albumex® 4 ‐ 500ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Immunoglobulin Group

CMV Immunoglobulin ‐ 30ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Hepatitis B Immunoglobulin ‐ 100IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Hepatitis B Immunoglobulin ‐ 400IU 3.00% 3.50% 4.00% 4.00%

Intragam® P ‐ 50ml 0.50% 0.00% 0.00% 0.00% 4.00% 4.00%

Intragam® P ‐ 200ml 0.50% 0.00% 0.00% 0.00% 4.00% 4.00%

Normal Immunoglobulin ‐ 2ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Normal Immunoglobulin ‐ 5ml 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Rh (D) Immunoglobulin ‐ 250IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Rh (D) Immunoglobulin ‐ 625IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Tetanus Immunoglobulin ‐ 250IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

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PRICE INCREASES


Tetanus Immunoglobulin ‐ 4000IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Zoster Immunoglobulin ‐ 200IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Clotting Factor Groups

Biostate® ‐ 250IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Biostate® ‐ 500IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

MonoFIX® ‐ VF ‐ 500IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

MonoFIX® ‐ VF ‐ 1000IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Prothrombinex™ ‐ 500IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

Thrombotrol® ‐ VF ‐ 1000IU 3.00% 3.50% 4.00% 4.00% 4.00% 4.00%

IMPORTED PRODUCTS

Ceprotin 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

Novoseven 3.00% 5.00% 5.00% 5.00% 5.00% 5.00%

Factor VII Concentrate 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

FEIBA inhibitor Treatment 7.00% 4.50% 5.00% 5.00% 5.00% 5.00%

Factor XI 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

WinRho® SDF 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

BeneFIX® (rFIX) 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

P a g e | 269

PRICE INCREASES


Recombinant Factor VIII (rFVIII) 2.00% 3.00% 3.00% 3.00% 3.00% 3.00%

Fibrogammin (Factor XIII Concentrate) 5.00% 4.50% 5.00% 5.00% 5.00% 5.00%

Imported IVIG 0.00% 4.50% 5.00% 5.00% 5.00% 5.00%

Source: National Blood Authority, 2011

A P P E ND I X 8

Scenario Data Tables

PROJECTED NOMINAL OUTLAYS BY SCENARIO ($M)

Year Baseline Trend

PBM Red

Cells PBM All IVIg Low

IVIg

Medium IVIg High

IVIg High +

Price

2010‐11 937$ 937$ 937$ 937$ 937$ 937$ 937$ 937$

2011‐12 980$ 1,025$ 980$ 961$ 981$ 982$ 984$ 989$

2012‐13 1,030$ 1,127$ 1,030$ 989$ 1,032$ 1,034$ 1,039$ 1,047$

2013‐14 1,084$ 1,242$ 1,084$ 1,020$ 1,086$ 1,091$ 1,099$ 1,112$

2014‐15 1,140$ 1,370$ 1,123$ 1,052$ 1,148$ 1,159$ 1,179$ 1,198$

2015‐16 1,207$ 1,524$ 1,170$ 1,091$ 1,219$ 1,239$ 1,274$ 1,314$

2016‐17 1,279$ 1,697$ 1,222$ 1,133$ 1,297$ 1,326$ 1,381$ 1,448$

2017‐18 1,355$ 1,893$ 1,275$ 1,176$ 1,379$ 1,419$ 1,498$ 1,601$

2018‐19 1,434$ 2,113$ 1,330$ 1,220$ 1,466$ 1,519$ 1,627$ 1,778$

2019‐20 1,518$ 2,362$ 1,407$ 1,266$ 1,557$ 1,626$ 1,769$ 1,983$

2020‐21 1,606$ 2,643$ 1,487$ 1,312$ 1,654$ 1,740$ 1,927$ 2,223$

2021‐22 1,699$ 2,961$ 1,572$ 1,361$ 1,757$ 1,863$ 2,103$ 2,505$

2022‐23 1,797$ 3,320$ 1,662$ 1,410$ 1,866$ 1,995$ 2,299$ 2,837$

2023‐24 1,901$ 3,727$ 1,757$ 1,462$ 1,982$ 2,137$ 2,518$ 3,228$

2024‐25 2,009$ 4,189$ 1,856$ 1,514$ 2,097$ 2,268$ 2,692$ 3,570$

2025‐26 2,124$ 4,712$ 1,961$ 1,569$ 2,219$ 2,406$ 2,882$ 3,960$

2026‐27 2,244$ 5,305$ 2,070$ 1,624$ 2,348$ 2,553$ 3,087$ 4,404$

2027‐28 2,371$ 5,979$ 2,186$ 1,681$ 2,483$ 2,708$ 3,311$ 4,912$

2028‐29 2,503$ 6,744$ 2,307$ 1,740$ 2,625$ 2,873$ 3,555$ 5,497$

2029‐30 2,643$ 7,614$ 2,434$ 1,801$ 2,775$ 3,048$ 3,821$ 6,170$

2030‐31 2,790$ 8,603$ 2,568$ 1,863$ 2,933$ 3,234$ 4,114$ 6,950$

2031‐32 2,944$ 9,730$ 2,709$ 1,926$ 3,099$ 3,431$ 4,435$ 7,855$

2032‐33 3,106$ 11,013$ 2,856$ 1,991$ 3,273$ 3,640$ 4,788$ 8,909$

2033‐34 3,274$ 12,475$ 3,009$ 2,057$ 3,455$ 3,860$ 5,177$ 10,138$

2034‐35 3,448$ 14,142$ 3,168$ 2,123$ 3,645$ 4,092$ 5,606$ 11,578$

2035‐36 3,630$ 16,045$ 3,334$ 2,191$ 3,843$ 4,338$ 6,081$ 13,269$

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PROJECTED REAL OUTLAYS* BY SCENARIO ($M)

* Deflated at 2.5% per annum

Year Baseline Trend

PBM Red


IVIg

Medium IVIg High

IVIg High +

Price

2010‐11 937$ 937$ 937$ 937$ 937$ 937$ 937$ 937$

2011‐12 956$ 1,000$ 956$ 956$ 957$ 958$ 960$ 965$

2012‐13 980$ 1,073$ 980$ 980$ 982$ 984$ 989$ 997$

2013‐14 1,006$ 1,154$ 1,006$ 1,006$ 1,009$ 1,013$ 1,020$ 1,032$

2014‐15 1,033$ 1,242$ 1,017$ 1,017$ 1,040$ 1,050$ 1,068$ 1,086$

2015‐16 1,067$ 1,347$ 1,034$ 1,034$ 1,078$ 1,095$ 1,126$ 1,161$

2016‐17 1,103$ 1,464$ 1,054$ 1,054$ 1,119$ 1,144$ 1,191$ 1,248$

2017‐18 1,140$ 1,592$ 1,072$ 1,072$ 1,160$ 1,194$ 1,260$ 1,347$

2018‐19 1,177$ 1,734$ 1,091$ 1,091$ 1,203$ 1,246$ 1,335$ 1,459$

2019‐20 1,215$ 1,891$ 1,126$ 1,126$ 1,247$ 1,302$ 1,417$ 1,588$

2020‐21 1,255$ 2,065$ 1,162$ 1,162$ 1,292$ 1,359$ 1,506$ 1,737$

2021‐22 1,295$ 2,256$ 1,198$ 1,198$ 1,339$ 1,420$ 1,603$ 1,909$

2022‐23 1,336$ 2,469$ 1,236$ 1,236$ 1,388$ 1,484$ 1,710$ 2,109$

2023‐24 1,379$ 2,704$ 1,274$ 1,274$ 1,438$ 1,550$ 1,827$ 2,342$

2024‐25 1,422$ 2,965$ 1,314$ 1,314$ 1,484$ 1,605$ 1,906$ 2,527$

2025‐26 1,466$ 3,253$ 1,354$ 1,354$ 1,532$ 1,661$ 1,990$ 2,734$

2026‐27 1,512$ 3,574$ 1,395$ 1,395$ 1,581$ 1,720$ 2,080$ 2,967$

2027‐28 1,558$ 3,929$ 1,436$ 1,436$ 1,632$ 1,780$ 2,176$ 3,228$

2028‐29 1,605$ 4,324$ 1,479$ 1,479$ 1,683$ 1,842$ 2,279$ 3,524$

2029‐30 1,653$ 4,763$ 1,523$ 1,523$ 1,736$ 1,907$ 2,390$ 3,860$

2030‐31 1,703$ 5,250$ 1,567$ 1,567$ 1,790$ 1,974$ 2,511$ 4,242$

2031‐32 1,753$ 5,793$ 1,613$ 1,613$ 1,845$ 2,043$ 2,641$ 4,677$

2032‐33 1,804$ 6,397$ 1,659$ 1,659$ 1,901$ 2,114$ 2,781$ 5,175$

2033‐34 1,855$ 7,069$ 1,705$ 1,705$ 1,958$ 2,187$ 2,934$ 5,745$

2034‐35 1,906$ 7,819$ 1,752$ 1,752$ 2,015$ 2,262$ 3,099$ 6,401$

2035‐36 1,958$ 8,654$ 1,798$ 1,798$ 2,073$ 2,340$ 3,280$ 7,157$

P a g e | 272

PROJECTED OUTLAYS BY SCENARIO: ALBUMIN ($M)

Year Baseline Trend

PBM Red


IVIg

Medium IVIg High

IVIg High +

Price

2010‐11 22.6$ 22.6$ 22.6$ 22.6$ 22.6$ 22.6$ 22.6$ 22.6$

2011‐12 23.8$ 24.5$ 23.8$ 23.3$ 23.8$ 23.8$ 23.8$ 23.8$

2012‐13 25.0$ 26.6$ 25.0$ 24.0$ 25.0$ 25.0$ 25.0$ 25.0$

2013‐14 26.3$ 29.0$ 26.3$ 24.8$ 26.3$ 26.3$ 26.3$ 26.3$

2014‐15 27.8$ 31.6$ 27.8$ 25.6$ 27.8$ 27.8$ 27.8$ 27.8$

2015‐16 29.3$ 34.5$ 29.3$ 26.5$ 29.3$ 29.3$ 29.3$ 29.3$

2016‐17 30.9$ 37.7$ 30.9$ 27.4$ 30.9$ 30.9$ 30.9$ 30.9$

2017‐18 32.6$ 41.1$ 32.6$ 28.3$ 32.6$ 32.6$ 32.6$ 32.6$

2018‐19 34.4$ 44.9$ 34.4$ 29.3$ 34.4$ 34.4$ 34.4$ 34.4$

2019‐20 36.2$ 49.0$ 36.2$ 30.2$ 36.2$ 36.2$ 36.2$ 36.2$

2020‐21 38.2$ 53.6$ 38.2$ 31.2$ 38.2$ 38.2$ 38.2$ 38.2$

2021‐22 40.2$ 58.5$ 40.2$ 32.2$ 40.2$ 40.2$ 40.2$ 40.2$

2022‐23 42.4$ 64.0$ 42.4$ 33.3$ 42.4$ 42.4$ 42.4$ 42.4$

2023‐24 44.6$ 69.9$ 44.6$ 34.3$ 44.6$ 44.6$ 44.6$ 44.6$

2024‐25 47.0$ 76.5$ 47.0$ 35.4$ 47.0$ 47.0$ 47.0$ 47.0$

2025‐26 49.5$ 83.6$ 49.5$ 36.6$ 49.5$ 49.5$ 49.5$ 49.5$

2026‐27 52.1$ 91.5$ 52.1$ 37.7$ 52.1$ 52.1$ 52.1$ 52.1$

2027‐28 54.8$ 100.1$ 54.8$ 38.9$ 54.8$ 54.8$ 54.8$ 54.8$

2028‐29 57.6$ 109.6$ 57.6$ 40.1$ 57.6$ 57.6$ 57.6$ 57.6$

2029‐30 60.6$ 120.0$ 60.6$ 41.3$ 60.6$ 60.6$ 60.6$ 60.6$

2030‐31 63.7$ 131.5$ 63.7$ 42.5$ 63.7$ 63.7$ 63.7$ 63.7$

2031‐32 67.0$ 144.0$ 67.0$ 43.8$ 67.0$ 67.0$ 67.0$ 67.0$

2032‐33 70.4$ 157.8$ 70.4$ 45.1$ 70.4$ 70.4$ 70.4$ 70.4$

2033‐34 73.9$ 173.0$ 73.9$ 46.5$ 73.9$ 73.9$ 73.9$ 73.9$

2034‐35 77.7$ 189.6$ 77.7$ 47.8$ 77.7$ 77.7$ 77.7$ 77.7$

2035‐36 81.5$ 208.0$ 81.5$ 49.2$ 81.5$ 81.5$ 81.5$ 81.5$

P a g e | 273

PROJECTED OUTLAYS BY SCENARIO: RED CELLS ($M)

Year Baseline Trend

PBM Red


IVIg

Medium IVIg High

IVIg High +

Price

2010‐11 291$ 291$ 291$ 291$ 291$ 291$ 291$ 291$

2011‐12 293$ 304$ 293$ 287$ 293$ 293$ 293$ 293$

2012‐13 312$ 335$ 312$ 299$ 312$ 312$ 312$ 312$

2013‐14 332$ 370$ 332$ 313$ 332$ 332$ 332$ 332$

2014‐15 354$ 408$ 336$ 327$ 354$ 354$ 354$ 354$

2015‐16 378$ 450$ 341$ 341$ 378$ 378$ 378$ 378$

2016‐17 405$ 497$ 347$ 358$ 405$ 405$ 405$ 405$

2017‐18 432$ 548$ 352$ 375$ 432$ 432$ 432$ 432$

2018‐19 461$ 605$ 357$ 393$ 461$ 461$ 461$ 461$

2019‐20 493$ 668$ 381$ 411$ 493$ 493$ 493$ 493$

2020‐21 525$ 737$ 407$ 429$ 525$ 525$ 525$ 525$

2021‐22 560$ 813$ 433$ 449$ 560$ 560$ 560$ 560$

2022‐23 597$ 897$ 462$ 469$ 597$ 597$ 597$ 597$

2023‐24 636$ 990$ 492$ 489$ 636$ 636$ 636$ 636$

2024‐25 678$ 1,092$ 524$ 511$ 678$ 678$ 678$ 678$

2025‐26 722$ 1,205$ 559$ 533$ 722$ 722$ 722$ 722$

2026‐27 768$ 1,330$ 594$ 556$ 768$ 768$ 768$ 768$

2027‐28 817$ 1,467$ 632$ 579$ 817$ 817$ 817$ 817$

2028‐29 868$ 1,619$ 672$ 604$ 868$ 868$ 868$ 868$

2029‐30 923$ 1,786$ 714$ 629$ 923$ 923$ 923$ 923$

2030‐31 981$ 1,971$ 759$ 655$ 981$ 981$ 981$ 981$

2031‐32 1,041$ 2,175$ 806$ 681$ 1,041$ 1,041$ 1,041$ 1,041$

2032‐33 1,105$ 2,400$ 855$ 708$ 1,105$ 1,105$ 1,105$ 1,105$

2033‐34 1,170$ 2,648$ 906$ 735$ 1,170$ 1,170$ 1,170$ 1,170$

2034‐35 1,238$ 2,922$ 958$ 762$ 1,238$ 1,238$ 1,238$ 1,238$

2035‐36 1,307$ 3,224$ 1,011$ 789$ 1,307$ 1,307$ 1,307$ 1,307$

P a g e | 274

PROJECTED OUTLAYS BY SCENARIO: IVIG ($M)

Year Baseline Trend

PBM Red


IVIg

Medium IVIg High

IVIg High +

Price

2010‐11 190$ 190$ 190$ 190$ 190$ 190$ 190$ 190$

2011‐12 194$ 206$ 194$ 190$ 195$ 196$ 198$ 203$

2012‐13 199$ 225$ 199$ 191$ 200$ 203$ 208$ 216$

2013‐14 204$ 247$ 204$ 192$ 207$ 211$ 219$ 232$

2014‐15 209$ 272$ 209$ 193$ 216$ 227$ 248$ 267$

2015‐16 221$ 310$ 221$ 200$ 233$ 252$ 288$ 327$

2016‐17 233$ 355$ 233$ 207$ 251$ 280$ 335$ 402$

2017‐18 247$ 408$ 247$ 214$ 271$ 311$ 389$ 493$

2018‐19 260$ 470$ 260$ 222$ 292$ 345$ 453$ 604$

2019‐20 275$ 543$ 275$ 229$ 314$ 383$ 526$ 741$

2020‐21 290$ 628$ 290$ 237$ 339$ 424$ 612$ 908$

2021‐22 307$ 727$ 307$ 246$ 365$ 471$ 711$ 1,112$

2022‐23 324$ 842$ 324$ 254$ 393$ 522$ 826$ 1,363$

2023‐24 342$ 978$ 342$ 263$ 423$ 578$ 959$ 1,669$

2024‐25 360$ 1,136$ 360$ 272$ 448$ 619$ 1,044$ 1,922$

2025‐26 380$ 1,320$ 380$ 281$ 476$ 663$ 1,138$ 2,216$

2026‐27 401$ 1,535$ 401$ 290$ 505$ 710$ 1,244$ 2,561$

2027‐28 423$ 1,786$ 423$ 300$ 535$ 761$ 1,363$ 2,965$

2028‐29 446$ 2,079$ 446$ 310$ 567$ 815$ 1,497$ 3,439$

2029‐30 470$ 2,421$ 470$ 320$ 602$ 875$ 1,648$ 3,997$

2030‐31 495$ 2,820$ 495$ 330$ 638$ 939$ 1,819$ 4,655$

2031‐32 521$ 3,286$ 521$ 341$ 676$ 1,008$ 2,012$ 5,432$

2032‐33 549$ 3,829$ 549$ 352$ 717$ 1,083$ 2,232$ 6,352$

2033‐34 578$ 4,462$ 578$ 363$ 760$ 1,164$ 2,482$ 7,443$

2034‐35 609$ 5,200$ 609$ 375$ 806$ 1,253$ 2,766$ 8,738$

2035‐36 641$ 6,062$ 641$ 387$ 854$ 1,348$ 3,091$ 10,280$

analysis of cost drivers and trends in the blood sector of cost drivers and trends in the blood...

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